Natasha Ali

Haemorrhagic manifestations and utility of haematological parameters in dengue fever: a tertiary care centre experience at Karachi.

A retrospective observational study of dengue fever was performed, including 210 patients (male:female ratio 1.6:1, ages 6–74 y, mean 29.7 y) attending the Aga Khan University Hospital, Karachi from January 2001 to December 2006. All included patients proved dengue IgM antibody positive. Of these, 19 (9%) showed increased haemoglobin/haematocrit levels on admission which remained elevated in 4 (2.1%) at the time of discharge. 56 patients (26.6%) had leucopenia and neutropenia and 77.1% (161) had thrombocytopenia at the time of admission; 2.5% (5) and 16.7% (35) had deranged PT and APTT, respectively. Atypical lymphocytes were seen in 109 patients (52%). Platelet transfusion was given in 45 (22.1%) cases. The majority of patients were discharged without any adverse sequelae. The fatality rate was 3.3% (n =7) and these patients died of dengue shock syndrome, while 196 (93.3%) recovered completely. Haematological parameters are an important clue and should be tested when a patient presents with symptoms suggestive of dengue fever.

Estimating window period blood donations for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus by nucleic acid amplification testing in Southern Pakistan.

Recently, strategic planning was initiated by the National Blood Transfusion Services Pakistan to improve its blood bank facilities. Emphasis has been placed on appropriate screening of blood products. Located in the southern region, Aga Khan University Hospital is a 700‐bed tertiary care academic institute with comprehensive blood banking. Screening of blood donors has been based on verbal screening and serologic testing to date. Additionally, the need of implementing nucleic acid testing (NAT) was considered in 2011 because of an upsurge in hepatitis epidemiology. The aim of this study was to analyze the efficacy of this additional donor screening program and to evaluate the impact of NAT on the yield and residual risk of transfusion‐transmissible viral infections.

Outcome of match related allogeneic stem cell transplantation procedures performed from 2004 till 2011

We present our initial experience of allogeneic stem cell transplant procedure performed between April 2004 and August 2011 for various haematological disorders. All patients with non-malignant and malignant haematological disorders with HLA matched donors were selected after pre-transplant workup. Ninety seven patients underwent the procedure. Most common indications for transplant were aplastic anaemia in n = 34 (35%), followed by β-Thalassemia major in n = 21 (21.6%) and chronic myeloid leukemia in n = 11 patients (11.3%). Primary graft failure present was present in 2.06%. Incidence of graft versus host disease (GvHD) in our patients was 34%. After median follow-up of five years the overall survival was 71.3% with a mean survival time of 51.2 ± 3.3 months.

Vibrio cholerae O1 bacteremia in Pakistan: analysis of eight cases.

Bacteremia caused by Vibrio cholerae O1 has been a rare phenomenon. We report on eight cases of V. cholerae O1 bacteremia from Pakistan which occurred during 1992-2008. Six of the cases were seen in children (two neonates and four infants) and seven of the eight patients were female. Urogenital malignancy, hepatitis B virus-associated end-stage liver disease, concurrent Campylobacter enteritis and prematurity were the underlying conditions in four patients. Two of the eight patients died and one was lost to follow up and this outcome may be due to prior immunity leading to less severe illness.

Bloodstream and central line isolates from hematopoietic stem cell transplant recipients: data from a developing country

Bloodstream infections (BSIs) and central line infections remain among the major causes of morbidity and mortality in transplant recipients because of prolonged neutropenia and mucosal damage. The objective of this study was to determine the frequency and outcome of bacterial and fungal isolates from patients undergoing allogeneic hematopoietic stem cell transplant.

Carrier detection for beta-thalassemia trait in general Pakistani population: a way forward

Abstract Objective To determine the frequency of beta-thalassemia minor in subjects with no family history of hemoglobinopathy. Methods Subjects were self-recruited on thalassemia day by advertisement through media. Those with indexed cases of beta-thalassemia major were excluded. Participants were interviewed regarding their marital status and screening of partners. Complete blood counts and peripheral smear review were performed on EDTA samples. Hemoglobin (Hb) electrophoresis was performed in cases with mean corpuscular volume (MCV) <76 fl, mean corpuscular Hb (MCH) <27 pg. HbA2 level >3.5% was diagnostic for beta-thalassemia trait. Results Out of 192 subjects, 11 were excluded based on family history of beta-thalassemia major and minor. Remaining 181 subjects (115 males and 66 females) were enrolled for further analysis. Median age was 27±9.7 years and included 101 married and 80 unmarried individuals. The mean Hb was 12.6 g/dl. MCV <76 fl and MCH <27 pg was seen in 29 subjects. Diagnosis of beta-thalassemia trait was made in 10 subjects (5.5%). Conclusion Though the carrier rate quoted is similar to previous studies, targeting families with indexed cases for screening might result in failure of carrier detection, since a large population would be overlooked. Implementation of national screening program is the need of the hour in Pakistan to evaluate the true burden of beta-thalassemia.

Bone marrow necrosis - initial presentation in sickle cell anemia.

Patient: Male, 20 Final Diagnosis: Sickle cell anemia Symptoms: Bone marrow necrosis • bone pain • fever • hepatomegaly • icterus • splenomegaly • weakness Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: In sickle cell disease, bone involvement is the commonest clinical presentation in the acute as well as chronic setting presenting as painful vaso-occlusive crisis and avascular necrosis, respectively. Other complications include bone marrow necrosis and infarction. Case Report: We report a case of a 20-year-old male who was referred for bone marrow evaluation due to symptoms of fever, weakness, and repeated episodes of bone pains. Bone trephine biopsy revealed multiple areas of central necrosis surrounded by fibroblasts. Conclusions: Recognition of necrosis through bone trephine biopsy is important for early initiation of therapy.

Reduced-intensity conditioning hematopoietic stem cell transplantation: looking forward to an international consensus

The treatment for hematological malignancies has excelled over the past decade. A vast number of hematological malignancies are now amenable to cure with hematopoietic stem cell transplants (HSCTs) [1]. Older patients with comorbidities are poor candidates for standard myeloablative conditioning (MAC). While myeloablative therapy remains the standard curative conditioning regimen in the treatment of malignant disorders such as acute myeloid leukemia, its use is limited to patients in the younger age group, and to those in good physical health. Therefore, the older population is generally unsuited to this form of treatment, even though most hematological malignancies are often diagnosed at the age of 70-80 years. The advent of reduced-intensity conditioning (RIC) has provided these patients with a viable treatment option. Prior to undergoing HSCT, patients are treated with a conditioning regimen. This not only decreases the tumor burden, but also maximizes the capability of the donor cells to engraft successfully by suppressing the patients immune system. Conditioning regimens vary in the amount of agent used. These compounds are often used at highly toxic dosage levels that are required to induce an immunocompromised state through a cytoreductive effect [2]. Over the past decade, conditioning regimens have considerably evolved with the development of RIC. These regimens are composed of reduced doses of cytotoxic agents in addition to a T-cell depleting agent [3]. The most commonly used regimens include fludarabine in combination with low-dose total body irradiation, or an alkylating agent such as busulfan, cyclophosphamide, or melphalan [3]. This treatment modality relies on a graft-versus-leukemia effect and has minimal associated toxicity. It is difficult to define RIC as it falls into an intermediate category between the MAC and the non-myeloablative regimens, since it does result in prolonged pancytopenia. Sources of donor cells include peripheral blood stem cells, bone marrow, and umbilical cord blood. Peripheral blood stem cells are more commonly used owing to the decreased engraftment time associated with their use [4]. Umbilical cord blood stem cells are a promising alternative source of stem cells with an associated 1-year survival rate of up to 40%, and a 9% incidence of grade III-IV acute graftversus-host disease (GVHD). However, studies have also reported a transplant-related mortality (TRM) rate of 39-48% associated with use of umbilical cord blood stem cells [5,6]. Studies assessing the influence of age on the outcomes of RIC treatment have not shown any significant association between the two. Patients in the age group >65 years have a reported non-relapse mortality (NRM) rate of 30% and 34% at 1 and 2 years respectively; whereas in the younger age group (40-54 years), the reported corresponding rates are 21% and 50% respectively [7]. A meta-analysis of results from 13 studies conducted by Zeng et al. [8] found no significant difference between MAC and RIC in terms of overall survival rate, event-free survival, and NRM. Furthermore, the incidence of GVHD was significantly lower with RIC. GVHD is an important cause of mortality associated with the MAC regimen due to the highly toxic doses of agents that are often necessary to eradicate diseased host cells from the bone marrow. The leading causes of death in patients treated with a MAC regimen are GVHD and toxicity. Thus, these findings call for extensive research on RIC regimens. The reported risk of TRM associated with MAC is 20%-60%, whereas RIC is known to be associated with higher overall survival and lower TRM at the same time [9]. A retrospective study on patients with MDS and AML treated with different conditioning regimens revealed a lower NRM in patients treated with RIC; however, there was also an increased risk of relapse in the first 12 months in these patients [10]. Although disease relapse continues to be a complication associated with both treatment regimens, RIC has a relatively higher incidence of relapse. This may be attributable to the additional host factors including, but not limited to, cytogenetics and disease status at the time of allogeneic HSCT. The use of RIC has opened up new channels to treat malignant hematological disorders in the elderly and patients with multiple comorbidities. With reduction in GVHD, in conjunction with decreased TRM, RIC provides a treatment option for patients who were previously unsuited for standard conditioning regimens. However, the RIC regimens may vary from one center to another and therefore it is conceivable that the differences in outcomes may be related to different procedures and/or different criteria used for decision making by individual physicians. This indicates the need for further studies, particularly in developing countries, so that an international consensus on protocols and guidelines for RIC may be reached.

Response to Imatinib Mesylate in Patients with Early Chronic Phase Chronic Myeloid Leukemia and Derivative Chromosome 9 Deletion or Clonal Evolution

Objectives: The significance of clonal evolution and derivative chromosome 9 in Philadelphia-positive CML is not fully characterized and studies have yielded conflicting results. After working on emergence of clonal evolution from our region, we continued to find out the response of Imatinib Mesylate on such cases of CML treated in our center. Materials and methods: We conducted a cross sectional, prospective analysis on response of Imatinib Mesylate on patients with Philadelphia positive chronic myeloid leukemia with clonal evolution treated from period of September 2007 till 2010. Patients were grouped on basis of cytogenetic analysis performed by conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques and followed for three years to see the response rate of imatinib mesylate. Results: We reported here the response rate in one hundred and two previously untreated cases of chronic myeloid leukemia (Philadelphia positive). Twelve patients (11.7%) exhibit derivative chromosome 9, three had trisomy 8, one with addition 15 and one had deletion 16. At follow-up of 30 months 78 cases were evaluable and 45% and 61% showed complete and major cytogenetic response respectively. There is no significant association of derivative chromosome 9 with the response of imatinib mesylate in our group. Conclusion: Imatinib mesylate is the first line therapy in chronic phase of CML but the role in patients with clonal evolution need to be established by larger group of patients.

Frequency and Outcome of Graft versus Host Disease after Stem Cell Transplantation: A Six-Year Experience from a Tertiary Care Center in Pakistan

Objective. The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan. Materials and Methods. Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 μg twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15 mg/m2 on day +1 followed by 10 mg/m2 on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification. Results. A total of 153 transplants were done from April 2004 to December 2011. Out of these were allogeneic transplants. There were females and males. The overall frequency of any degree of graft versus host disease was 34%. Acute GvHD was present in patients while had chronic GvHD. Grade II GvHD was present in patients while grade III and IV GvHD was seen in patients each. Acute myeloid leukemia and chronic myeloid leukemia were most commonly associated with GvHD. The mortality in acute and chronic GvHD was 8.8% and 12% respectively. Conclusion. The frequency of graft versus host disease in this study was 34% which is lower compared to international literature. The decreased incidence can be attributed to reduced diversity of histocompatibility antigens in our population.