Guideline for the first-line management of Classical Hodgkin Lymphoma - A British Society for Haematology guideline.

This guideline was compiled according to the British Society for Haematology (BSH) process at BSH Guidelines Process 2016 (b-s-h.org.uk). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Recommendations are based on a review of the literature using Medline, PubMed/Medline and Cochrane searches beginning from 2013 up to January 2021. The following search terms were used: [Hodgkin lymphoma OR Hodgkin disease] NOT non-Hodgkin; AND [chemotherapy OR radiotherapy]; AND [elderly]; AND [teenage OR adolescent OR young adult]; AND [pregnancy]. Filters were applied to include only publications written in English, studies carried out in humans, clinical conferences, congresses, clinical trials, clinical studies, meta-analyses, multicentre studies and randomised controlled trials. References pre-2013 were taken from the previous version of this guideline.1 Review of the manuscript was performed by the British Society for Haematology (BSH) Guidelines Committee Haematology Oncology Taskforce, the BSH Guidelines Committee and the Haematology Oncology sounding board of BSH.

Diagnostic dilemma of Hodgkin's lymphoma versus tuberculosis: a case report and review of the literature.

BACKGROUND: Hodgkin's Lymphoma (HL) is a rare malignancy characterised histologically by the presence of Reed-Sternberg cells. Diagnosis of lymphomas can be difficult due to broad, non-specific presentations of disease, which can be similar to several other conditions ranging from infective, inflammatory or malignant causes, with one of the most common differentials being tuberculosis (TB). We aim to highlight the diagnostic dilemma of TB versus lymphoma with an atypical presentation of HL and explored areas for further research and improvement with a non-systematic literature review using MEDLINE database and Google Scholar. Written consent was obtained from the patient in compliance with ethical guidelines. CASE PRESENTATION: A 23-year-old Asian female initially presented to rheumatology with over a one-year history of neuropathic pain, alongside abnormal white cell count and inflammatory markers. This was investigated with magnetic resonance imaging resulting in an incidental finding of mediastinal mass and pulmonary infiltrates. An initial diagnosis of TB was made despite testing negative for acid-fast bacilli and anti-tubercular treatment was commenced. Four months later, following clinical deterioration and further investigations, a mediastinal biopsy assisted in diagnosing Stage IV HL. CONCLUSIONS: Lymphoma is often misdiagnosed as TB, prolonging time to treatment and may adversely impact patient prognosis due to disease progression. Existing TB guidelines for smear-negative cases are not clear when to consider alternative diagnoses. In smear-negative TB, lymphoma should be considered as a differential and definitive diagnostic tests such as molecular testing and histological examination of biopsies should be considered earlier in the diagnostic work-up to prevent diagnostic delay.

Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia.

Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n = 7) or a myeloid neoplasm with eosinophilia (n = 20) had been made prior to the detection of STAT5B N642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0-4) with 4 cases having STAT5B N642H as a sole abnormality. STAT5B N642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1 mutations (9/27; 33%) or STAT5B N642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P < 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy.

Risk stratification in febrile neutropenic episodes in adolescent/young adult patients with cancer.

BACKGROUND: Risk-stratified management of febrile neutropenia (FN) allows intensive management of high-risk cases and early discharge of low-risk cases. Most risk stratification systems predicting severe infection from admission variables have been derived from childhood or adult populations and consequently their value in adolescents/young adults (AYA) may vary. Our objective was to determine their value in this population. METHODS: Data from the 'predicting infectious complications in children with cancer' (PICNICC) individual participant data collaboration were used to evaluate six previously described risk stratification schema in the AYA population. Complete case analyses were undertaken for five 'paediatric' rules, with imputation for specific missing variables of the 'adult' rule. The predictive performance of the rules or the outcome microbiologically defined infection (sensitivity, specificity and predictive values) were compared. RESULTS: Among the 5,127 episodes of FN in 3,504 patients in the PICNICC collaboration data set, 603 episodes of FN from 478 patients in 20 studies were of patients 16-25 years old. The six rules demonstrated variable sensitivity (33-96%) and specificity (13-83%). Their overall discriminatory ability was poor (area under the receiver operator curve estimates 0.514-0.593). CONCLUSIONS: Both paediatric and adult FN risk stratification schema perform poorly in AYA with cancer. An alternative rule or clinical recognition of their limitations is required.

Late mortality, secondary malignancy and hospitalisation in teenage and young adult survivors of Hodgkin lymphoma: report of the Childhood/Adolescent/Young Adult Cancer Survivors Research Program and the BC Cancer Agency Centre for Lymphoid Cancer.

Late complications affecting Hodgkin lymphoma (HL) survivors are well described in paediatric and adult-based publications. This study determined the late morbidity and mortality risk for 442 teenage and young adult (TYAs) 5-year HL survivors, diagnosed at 15-24 years of age between 1970 and 1999, identified from the British Columbia Cancer Registry. Treatment details were abstracted from charts. Survivors and a matched comparison cohort were linked to provincial administrative health datasets until December 2006 and regression analysis was performed, providing risk ratios regarding mortality, secondary malignancy and morbidity causing hospitalisation. Sixty (13·6%) survivors experienced late mortality with excess deaths from secondary cancer [standardised mortality ratio (SMR) 18·6; 95% confidence interval (CI) 11-29·4] and non-malignant disease (SMR 3·6; 95% CI 2·2-5·5). Excess secondary cancers (standardised incidence ratio 7·8; 95% CI 5·6-10·5) were associated with radiotherapy [Hazard ratio (HR) 2·7; 95% CI 1-7·7] and female gender (HR 1·8; 95% CI 1-3·4). Of 281 survivors treated between 1981 and 1999, 143 (51%) had morbidity resulting in hospitalisation (relative risk 1·45; 95% CI 1·22-1·73). Hospitalisation significantly increased with combined modality therapy, chemotherapy alone and recent treatment era. TYA HL survivors have excess risk of mortality and secondary malignancy continuing 30 years from diagnosis. Radiotherapy is associated with secondary malignancy and current response-adapted protocols attempt to minimise exposure, but late morbidity causing hospitalisation remains significant.

Intra-arterial methylprednisolone for severe steroid refractory gastrointestinal graft-versus-host disease.

Acute graft versus host disease (GVHD) is a significant complication of bone marrow transplantation with approximately half of patients being refractory to steroids. There are numerous second-line systemic immunosuppressive treatments but the overall prognosis is poor and these therapies are associated with high mortality due to infection. An alternative approach to systemic treatment for GVHD is targeted delivery of immunosuppression. We present two pediatric cases with steroid-refractory gastrointestinal GVHD who clinically responded to intra-arterial steroid administration. We also review the literature regarding this treatment modality with a particular emphasis in children.

Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma.

The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4(+) T-cells (<10 to >50 % of all lymph node cells) and PD-1(hi) cells (0.1 to 1.5 % of all cells). CD4(+) T-cells can be distributed in clusters or more diffusely and PD-1(hi) cells, but not FoxP3(+) cells, are found in rosettes around lymphoma cells. Cases with high CD4(+) T-cell numbers tended to have higher numbers of both PD-1(hi) and FoxP3(+) cells. Cases with total CD4(+) T-cell, PD-1(hi) and FoxP3(+) numbers above the median associate with better clinical outcome. Overall, we demonstrate that infiltration by CD4(+) T-cells, including both FoxP3(+) and PD-1(hi) subsets, correlates with prognosis in DLBCL. In distinction to previous reported series, patients (91 %) were treated with rituximab-containing regimens, suggesting that the effects of CD4+ T-cell infiltration are maintained in the rituximab era. This work suggests that determinants of total CD4(+) T-cell infiltration, either molecular characteristics of the lymphoma or the patients' immune system, and not individual T-cell subsets, correlate with clinical outcome.