Prospective identification of variables as outcomes for treatment (PIVOT): study protocol for a randomised, placebo-controlled trial of hydroxyurea for Ghanaian children and adults with haemoglobin SC disease.

BACKGROUND: Haemoglobin SC (HbSC) is a common form of sickle cell disease (SCD), especially among individuals of West African ancestry. Persons with HbSC disease suffer from the same clinical complications and reduced quality of life that affect those with sickle cell anaemia (HbSS/Sß0). Retrospective anecdotal data suggest short-term safety and benefits of hydroxyurea for treating HbSC, yet rigorous prospective data are lacking regarding optimal dosing, clinical and laboratory effects, long-term safety and benefits, and appropriate endpoints to monitor. Prospective Investigation of Variables as Outcomes for Treatment (PIVOT) was designed with three aims: (1) to measure the toxicities of hydroxyurea treatment on laboratory parameters, (2) to assess the effects of hydroxyurea treatment on sickle-related clinical and laboratory parameters, and (3) to identify study endpoints suitable for a future definitive phase III trial of hydroxyurea treatment of HbSC disease. METHODS: PIVOT is a randomised, placebo-controlled, double blind clinical trial of hydroxyurea. Approximately 120 children and 120 adults ages 5-50 years with HbSC disease will be enrolled, screened for 2 months, and then randomised 1:1 to once-daily oral hydroxyurea or placebo. Study treatment will be prescribed initially at 20 ± 5 mg/kg/day with an opportunity to escalate the dose twice over the first 6 months. After 12 months of blinded study treatment, all participants will be offered open-label hydroxyurea for up to 4 years. Safety outcomes include treatment-related cytopenias, whole blood viscosity, and adverse events. Efficacy outcomes include a variety of laboratory and clinical parameters over the first 12 months of randomised treatment, including changes in haemoglobin and fetal haemoglobin, intracranial arterial velocities measured by transcranial Doppler ultrasound, cerebral oxygenation using near infrared spectrometry, spleen volume and kidney size by ultrasound, proteinuria, and retinal imaging. Exploratory outcomes include functional erythrocyte analyses with ektacytometry for red blood cell deformability and point-of-sickling, patient-reported outcomes using the PROMIS questionnaire, and 6-min walk test. DISCUSSION: For children and adults with HbSC disease, PIVOT will determine the safety of hydroxyurea and identify measurable changes in laboratory and clinical parameters, suitable for future prospective testing in a definitive multi-centre phase III clinical trial. TRIAL REGISTRATION: PACTR, PACTR202108893981080. Registered 24 August 2021, https://pactr.samrc.ac.za.

Immunophenotypic characterisation of non-Hodgkin lymphomas at a tertiary hospital in Ghana.

Background: Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of clonal lymphoid tumours originating from lymphocytes. They constitute about 90% of an estimated 3%-4% worldwide distribution of malignant lymphomas among various cancers. Despite the continuous rise and associated deaths, research on NHLs, and in particular the area of immunophenotypic spectrum is limited in Ghana and sub-Saharan Africa. Methods: A retrospective, descriptive study in which archived tissue blocks of histologically diagnosed NHLs at a tertiary hospital in Accra, Ghana, were used. Antigenic phenotypes were determined by immunohistochemistry. Results: A total of 66 cases of NHLs, with a mean age of 50.2 ± 16.1 years, were selected for the study. Among the targeted markers, cluster of differentiation 20 (CD20) was the most commonly expressed in 89.4% (59) cases. Immunohistochemistry studies revealed a greater proportion of B cell lymphomas of 89.4%. Five subtypes were successfully identified, of which diffuse large B cell lymphoma constitutes the predominant group (40.9%). A significant association was observed between phenotypic cell types and outcomes of NHLs (p = 0.011). Conclusion: Adult NHLs were mostly due to the malignant transformation of B cells with diffuse large B cell lymphoma being the commonest subtype. The present study therefore serves as preliminary data for further research towards the adoption of an improved treatment regimen and management of NHLs.

Bleomycin-induced pneumonitis in a young Ghanaian male with Hodgkin's Lymphoma.

We report a case of a young Ghanaian male who developed Bleomycin Induced Pneumonitis (BIP) after being treated for Hodgkin's Lymphoma. Pulmonary toxicity is the most feared complication of bleomycin therapy despite its effectiveness in achieving cure in patients with Hodgkin's lymphoma and germ cell tumors. BIP has a significant mortality rate if detected late and a high index of suspicion is required in all patients on bleomycin-based therapies with sudden onset of respiratory symptoms.

Steroid-induced dysglycaemia in patients with haematological disorders a ten-year review in a tertiary hospital in Ghana.

BACKGROUND: Glucocorticoids (steroids) play a key role in the management of multiple medical conditions including haematological disorders. This study looked at the prevalence of steroid induced dysglycaemia in patients with haematological disorders receiving steroids as part of their treatment with the view of modifying its use and selection of patients where necessary. METHODS: A retrospective review of haematology patients on treatment regimens including steroids. Information extracted included, demographic characteristics, clinical information such as age, gender, haematological disorder, type of steroid, daily and cumulative dose of steroid, duration of therapy, family history of diabetes and alcohol use. RESULTS: The case records of 351 haematology patients were reviewed. However, eight patients with dysglycaemia before therapy were excluded. The median age of patients was 51.0 ± 26.0(IQR: Interquartile Range) years, with an age range of 13 to 87 years, and a female: male ratio of 1.2: 1 (p= 0.778). The prevalence of Steroid-Induced Dysglycaemia (SID) was 3.79% with a mean diagnosis interval of 8.8 + 2.1 months. Overall, 245 (71.4%) patients were on continuous steroids. Among the 13 patients who developed SID, 11 (84.6%) were on continuous steroids. In the majority of the patients (97.1%) there was no family history of diabetes in a first degree relative. Significant differences were found between patients with normoglycaemia and those with dysglycaemia with respect to age (p=0.049) and duration of steroid therapy (p=0.024). CONCLUSION: The prevalence of steroid-induced dysglycaemia is relatively low among Ghanaian patients with haematological disorders on steroid based chemotherapy. FUNDING: None declared.

Lung Function Abnormalities in Sickle Cell Anaemia.

BACKGROUND: Abnormalities in lung function tests have been shown to commonly occur in a majority of patients with sickle cell disease (SCD) even at steady state. The prevalence and pattern of these lung function abnormalities have been described in other populations but this is unknown among our sickle cell cohort. There is generally little information available on risk factors associated with the lung function abnormalities and its relevance in patient care. METHOD: This was an analytical cross-sectional study involving 76 clinically stable, hydroxyurea-naive adult Hb-SS participants and 76 nonsickle cell disease (non-SCD) controls. A structured questionnaire was used to obtain sociodemographic data and clinical history of the participants. Investigations performed included spirometry, pulse oximetry, tricuspid regurgitant jet velocity (TRV) measurements via echocardiogram, complete blood counts, free plasma haemoglobin, serum urea, and creatinine. RESULTS: Weight, BMI, mean FVC, and FEV1% predicted values were comparatively lower among the Hb-SS patients (p < 0.001). Abnormal spirometry outcome occurred in 70.4% of Hb-SS patients, predominantly restrictive defects (p < 0.001), and showed no significant association with steady-state Hb, WBC count, free plasma haemoglobin, frequency of sickling crisis, chronic leg ulcers, and TRV measurements (p > 0.05). The mean oxygen saturation was comparatively lower among Hb-SS patients (p < 0.001). CONCLUSION: Measured lung volumes were significantly lower in Hb-SS patients when compared to non-SCD controls and this difference was not influenced by anthropometric variance. Lung function abnormalities, particularly restrictive defects, are prevalent in Hb-SS patients but showed no significant association with recognized markers of disease severity.

Sjögren's and plasma cell variant Castleman disease: a case report.

Castleman disease is a rare cause of lymphoid hyperplasia and may result in localized symptoms or an aggressive, multisystem disorder. It can mimic other diseases like lymphoma or tuberculosis. It classically presents as a mediastinal mass that involves the lymphatic tissue primarily but can also affect extra lymphatic sites including the lungs, larynx, parotid glands, pancreas, meninges, and muscles. In HIV and HHV8-negative patients with idiopathic multi-centric Castleman disease, pathogenesis may involve autoimmune mechanisms. We highlight and report a case of a 34-year-old Ghanaian female who was successfully diagnosed and managed for Sjögren's as well as plasma cell variant Castleman disease with combination chemotherapy and rituximab followed by eighteen months maintenance therapy with pulse chlorambucil and prednisolone and three monthly rituximab.