Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma: an open-label Phase II feasibility study.

PURPOSE: Sorafenib is considered a standard of care in advanced hepatocellular carcinoma (HCC). Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile may prove beneficial in advanced HCC. The primary objective was to evaluate the efficacy and safety of a sorafenib and gemcitabine combination in patients with advanced HCC. METHODS: This was a non-randomized, open-label, single-arm, multi-centric Phase II study conducted in Pakistan where 30 treatment-naive patients aged between 26 and 73 years with Child-Pugh score A or B were treated with sorafenib (400 mg oral) twice daily for 16 weeks along with gemcitabine (1000 mg/m(2) intravenous) administered on day 1 and day 8 of a four-week cycle for 16 weeks. RESULTS: Of the 18 patients (60%) who completed all four cycles of treatment, eight patients had stable disease, two had partial response, and eight had progressive disease. There was no complete response. The most common (≥10% patients) treatment-emergent adverse events were gemcitabine-related thrombocytopenia (40%) followed by sorafenib-related hand-foot skin reaction and anorexia (33% each). CONCLUSION: The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.

A multicentre phase-II feasibility study evaluating gemcitabine/vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma.

OBJECTIVE: To determine the efficacy and toxicity of Gemcitabine, Vinorelbine and Prednisolone (GVP) salvage chemotherapy in relapsed / refractory Hodgkin's Lymphoma (HL). STUDY DESIGN: A phase-II non-randomized single arm study. PLACE AND DURATION OF STUDY: This study was conducted at Combined Military Hospital and Medical College Lahore, Mayo Hospital, King Edward Medical University, Lahore, Allied Hospital, Punjab Medical College, Faisalabad and Combined Military Hospital, Rawalpindi, from January 2007 to December 2007. METHODOLOGY: Fifty adult patients with relapsed/refractory HL, adequate marrow reserve, hepatorenal and pulmonary functions, with radiological measurable disease and Karnofsky performance status of 0 - 2 non-candidates for stem cell transplantation, were enrolled. Four 28 days cycles of GVP (Gemcitabine 1000 mg/m2, Vinorelbine 30 mg/m2 on day 1 and 8 intravenously with oral Prednisolone 100 mg/day on day 1 - 5) were given. Response evaluation done according to Cotswolds meeting recommendations and toxicity was evaluated with NCI-CTC (National Cancer Institute - Common Terminology Criteria for adverse events v 3.0). RESULTS: Forty patients completing 4 cycles of GVP, 14 refractory/early relapse and 26 late relapsed (one year postprimary treatment with ABVD) were available for evaluation. The overall response (CRu+PR) rate was 77.5% with better response 85% in late relapsed patients. Haematological toxicity was most common and seen in 70% of cases. CONCLUSION: GVP is well-tolerated regimen with high response rate and needs to be tested in late relapsed HL.

Presentating phases of chronic myeloid leukaemia.

OBJECTIVE: To determine the frequency of three phases of chronic myeloid leukaemia at first presentation. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Oncology, Combined Military Hospital (CMH), Rawalpindi, from June 2006 to December 2007. METHODOLOGY: Forty-five patients of either gender with Chronic Myeloid Leukaemia (CML) at their first presentation in outpatient department were included in the study by consecutive sampling technique. All patients were diagnosed on blood complete picture and bone marrow examination including aspiration, trephine and cytogenetics at Armed Forces Institute of Pathology (AFIP). Each phase was defined on the basis of World Health Organization (WHO) criteria. RESULTS: Out of 45, there were 31 (68.9%) male and 14 (31.1%) female patients. The mean age of presentation was 37.9 years. The pattern of presentation revealed 35 (77.8%) in Chronic Phase (CP), 7 (15.5%) in Accelerated Phase (AP) and 3 (6.7%) in Blast Crisis (BC). Philadelphia chromosome was detected in 39 (86.7%) cases on culture method. Splenomegaly was observed in 37 (82.2%) patients. The mean total leukocyte count, platelet count, haemoglobin and marrow blast were 214.3 x 10(9)/L, 551.4 x 10(9)/L, 9.94 g/dl and 9.3% respectively. CONCLUSION: CML presented at a younger age in the chronic phase.

Frequency of bone marrow involvement in Hodgkin's lymphoma on first presentation.

OBJECTIVE: To determine the frequency of bone marrow involvement in patients of Hodgkin's lymphoma on first presentation at oncology department. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Oncology Department, Combined Military Hospital, Rawalpindi, from April 2006 to February 2007. METHODOLOGY: Thirty five patients of Hodgkin's lymphoma diagnosed on lymph node biopsy presenting for the first time at Oncology Department, Combined Military Hospital, Rawalpindi were included. They were admitted in the ward and evaluated with history, physical examination and staging investigations. Bone marrow trephine biopsy was performed in all patients. Descriptive statistics were used to analyze data. RESULTS: On clinical and radiological evaluation, 8 patients (22.9%) had clinical stage (CS), 12 (34.3%) had CS II, 9 (25.7%) had CS III and 6 (17.1%) had CS IV. The microscopic appearance in bone marrow trephine examination showed lymphoma infiltrates in 6 (17.14%) patients and chronic disorder in 29 (82.85%) patients. Among patients with bone marrow infiltration, one had CS II disease, three had CS III disease and two had CS IV disease. One patient had bone marrow infiltration as the only manifestation of disease. CONCLUSION: Bone marrow involvement was seen in patients with Hodgkin's lymphoma clinical stage II or higher.

Microalbuminuria: association with ischaemic heart disease in non-diabetics.

BACKGROUND: In view of the high morbidity and mortality associated with ischemic heart disease (IHD), the estimation of individual cardiovascular risk over and above the assessment of classic risk factors, such as age, hypercholesterolemia and hypertension, is an important prerequisite for focusing preventive measures and therapeutic measures. Microalbuminuria (MA) as a marker of IHD in nondiabetics is currently under international debate. The present descriptive study undertaken at Combined Military Hospital, Lahore was aimed to determine the frequency of MA in nondiabetic IHD patients. METHODS: One hundred consecutive non diabetic patients with IHD (73 males, 27 females). Patients showing clinical albumiuria and with other causes of proteinuria were excluded. Urinary albumin in first morning sample was estimated by immunoturbidimetry method. Albumin to creatinine ratio (ACR) was calculated as mg/g. RESULTS: The frequency of MA (ACR >30 mg/g) was 37% in patients. Frequency was highest in older age bracket for both genders. The mean ACR was 131.8 +/- 66.2 mg/g. Significant difference was observed in mean MA level among different age groups. CONCLUSION: MA is common in nondiabetics patients with IHD. The mean level of MA was higher in older patients.