Types of paraproteinemia in patients with multiple myeloma: A cross-sectional study.

OBJECTIVE: To determine the types of paraproteins in patients with multiple myeloma in a tertiary care setting. METHODS: The cross-sectional study was conducted at the Liaquat National Hospital, Karachi, from November 2015 to May 2016, and comprised patients with multiple myeloma selected using consecutive, non-probability sampling technique. Detailed history was taken and immunofixation assay was conducted to assess the type of paraproteins in the patients. Data was recorded on a proforma and analysed using SPSS 22. RESULTS: Of the 87 patients, 62(71.3%) were males and 25(28.7%) were females. The overall mean age was 57.41±10.53 years. Of the total, 52(71.3%), patients had Immunoglobulin G kappa and 61(70%) had Immunoglobulin A kappa paraprotein. CONCLUSIONS: The most common types of paraprotein was found to be Immunoglobulin G kappa followed by Immunoglobulin A kappa.

Disease staging according to international scoring system in newly diagnosed patients with multiple myeloma.

OBJECTIVE: To determine the frequency of disease staging according to international scoring system in patients who are newly diagnosed with Multiple Myeloma (MM) at a tertiary care hospital at Karachi. METHODS: This single center, non probability consecutive, cross sectional study was conducted from Nov 11, 2015 to May 11, 2016. After taking informed written consent, detailed history was taken and serum ß2 microglobulin and albumin levels were checked to assess the study outcome variable i.e. stage of MM. All the collected information was entered in the prescribed performa. RESULTS: Eighty newly diagnosed patients with multiple myeloma as per inclusion criteria were included. Sixty seven (83.75%) were male and 13(16.25) were females, with mean age of 58.35+10.077 years. Twenty seven patients (33.75%) were found to have stage-I disease, in 23 (28.75%) stage-II and stage-III in 30 (37.5%). CONCLUSION: Multiple myeloma is relatively common in 5th decade, with male predominance. International Staging System have great potential for characterizing and stratifying multiple myeloma and revealed a predominance of advanced stage III disease in our setting.

Frequency of TP53 Mutation in B-Cell Chronic Lymphocytic Leukaemia and its Association with Lymphocyte Doubling Time.

OBJECTIVE: To determine the frequency of TP53 mutation at diagnosis of B-cell Chronic Lymphocytic Leukaemia (B-CLL) in Pakistani patients, and to investigate whether lymphocyte doubling time (LDT) of less than 1 year could be used as a surrogate marker for TP53 mutation. STUDY DESIGN: A cross-sectional descriptive study. Place and Duration of the Study: Department of Haematology, Liaquat National Hospital, from January 2020 to December 2022. METHODOLOGY: Patients diagnosed with B-CLL based on the criteria set by International Workshop on Chronic Lymphocytic Leukaemia were included in the study. Clinico-haematological parameters were recorded, and TP53 mutation analysis was performed by fluorescence in situ hybridisation. Patients were followed every 3-6 months after diagnosis with the recent complete blood count (CBC) reports to record CBC parameters and calculate LDT. RESULTS: A total of 128 B-CLL cases were evaluated, with a mean age of 62 years. Among these cases, 10 patients (7.8%) tested positive for TP53 mutation, while 118 patients (92.2%) tested negative. During the follow-up period, 26 patients were lost to follow-up, with only one patient from the TP53 positive group. In the TP53 positive group, 55.6% (n=5/9) patients had an LDT of less than 1 year, indicating aggressive disease compared to 30.1% (n=28/93) patients in the negative group (p <0.1). CONCLUSION: TP53 mutations may be associated with shorter LDT, indicating aggressive disease. Further research is needed to fully comprehend the relationship between TP53 mutation and LDT in B-CLL. KEY WORDS: TP53 mutation, B-Cell chronic lymphocytic leukaemia (B-CLL), Lymphocyte doubling time (LDT).

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.

In Vitro Leukoagglutination: A Rare Hematological Cause of Spurious Leukopenia.

Leukopenia secondary to leukocytic agglutination is caused by an ethylene diamine tetra acetic acid (EDTA) which may appear in both benign and malignant states. Ethylene diamine tetra acetic acid induced platelets clumping in peripheral blood has been well established, but invitro leukocytic aggregation is very rarest hematological finding. Pseudo-leukopenia resulting from leukoagglutinins has been reported in the cirrhotic state, infections, autoimmune disorders, uremia, in immunosuppressed state or in various malignancies. Though the condition seems to be benign but very important to be detected as these artifactual findings lead to unnecessary investigations and remarkably changed the overall management plan. Here we report the case of a young patient with this rare finding who was admitted to our hospital with progressive labor pains. The analysis of ethylene diaminetetraacetic acid (EDTA), anticoagulated blood was done on automated hematology analyzer reveals leukopenia. The peripheral smear examination revealed multiple aggregates of leukocytes. On repeat sampling in citrate anticoagulant, the complete blood count showed total leukocytic count of 16.5x109/L with absolute neutrophilic count of 11.5x109/L. This is a rare case of spurious leukopenia secondary to in-vitro leukocytic agglutination provoked by EDTA anticoagulant.

Clinico-hematological profile of patients with B-chronic lymphoid leukemia in Pakistan.

BACKGROUND: Chronic lymphoid leukemia (CLL) is not an uncommon hematological malignancy which primarily affects elderly individuals. It is more common in developed world than in developing countries. The rational of this study was to determine the clinico-hematological profile in Pakistan. MATERIALS AND METHODS: In this prospective cross sectional study, sixty patients with CLL were enrolled from January 2011 to June 2013. Data were analyzed with SPSS version 21. RESULTS: The mean age was 59.0±9.2 years (range 40-82) and the male to female ratio was 2.1:1. Peak age group was 60-70 years (38.3%) and 18.3% were under 50 years old. Major complaints were weakness (51.7%), fever (18.3%) and abdominal discomfort (13.3%). Main clinical findings were splenomegaly (46.6%), lymphadenopathy (36.6%) and pallor (26.7%). Some 16.7% were diagnosed incidentally. The mean hemoglobin was 10.8±2.4 g/dl, with a total leukocyte count of 91.5±87.8x10(9)/l and platelets 197.8±103.2x10(9)/l. Anemia and thrombocytopenia were seen in 26.7% and 21.7% of cases, respectively. High LDH and hyperuricemia were detected in 15% each and elevated serum creatinine was seen in 11.6%. According to Rai staging 11.6% were in stage 0, 13.3% stage 1, 26.7% each for stage II and stage III while 21.7% patients were in stage IV. CONCLUSIONS: CLL in our patients in Pakistan, unlike in the West, is seen in a relatively young population with male predominance. Primarily disease is of B- cell origin and about 2/3 of the patients present at advanced stage.

Clinico-pathological features and outcomes in chronic phase chronic myeloid leukemia patients treated with hydroxyurea.

OBJECTIVE: To study the clinico-pathological features and major outcomes in patients with chronic myeloid leukemia, chronic phase, treated with hydroxyurea. METHODS: This is a single centre study extending from January 1997 to June 2003. Data were retrieved from the patients' records on predetermined performance and analyzed. Patients were primarily diagnosed on the basis of clinical findings, complete blood counts and leukocyte alkaline phosphate (LAP) scores. Bone marrow/trephine and genetic studies were conducted where appropriate. Patients were primarily treated with capsule hydroxyurea 30-50/ kg/day. RESULTS: One hundred and seventy six patients, 104 (59%) male and 72 (41%) females were included in the study. The median age at diagnosis was 39 years (range 11 to 66 years). The median delay in diagnosis was 156 days (range 30 to 360 days). Eighty four patients (47.7%) presented with pain/discomfort in the left hypochondrium. The mean hemoglobin, white blood cell count and platelet counts were 10.3 g/dl, 141,000/UL and 341,000/UL respectively associated with a low LAP score. Hyper-leucocytosis was observed in 19 (10.7%) cases. LDH values above 1,000 ug/l were observed in 38 (21.5%) cases and creatinine above 1.5 ug/l in 21 (12%) cases. All patients tested, were positive for Philadelphia chromosome and bcr-abl transcripts. At the close of the study, disease advancement was observed in 76 (43.2%) cases, of which 35 (20%) transformed to acute leukemia. One hundred and forty three patients (81%) were alive at the close of the study. One hundred and two (58.4%) patients were in chronic phase, 22 (12.5%) in accelerated phase and 19 (10.7%) in blast crisis. Disease progression remained the major cause of death and was seen in 29 (16.4%) patients. CONCLUSION: In the study population, CML was observed in a younger age group with significant delay in definitive diagnosis. Clinico-pathological features and major outcomes, however, appear comparable to published data.