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

INTRODUCTION: 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. MATERIALS AND METHODS: This study was conducted at the Aga Khan University and Hospital's bone marrow transplant unit. All patients who underwent an allogeneic stem cell transplant with matched sibling/parent donor were included. The study period ranged from April 2004 to December 2012. Transplantation was performed according to institutional protocols. All patients were admitted in single rooms with positive pressure and high-efficiency particulate air filters. Ciprofloxacin, fluconazole, and valaciclovir were used for standard prophylaxis, which was started at the time of conditioning. All blood cultures were obtained at clinical suspicion of systemic infection, mainly documented as fever (temperature of >38.5°C). BSIs and line infections were defined as isolation of bacterial or fungal pathogen from at least one blood/central line culture. RESULTS: In total, 101 of 108 patients developed febrile neutropenia. In the 101 patients, 245 documented febrile episodes occurred. There were 40 culture-positive episodes and 205 culture-negative episodes. Of these 40 culture-positive episodes, 22 patients had bloodstream isolates and 18 had central line isolates. The median ± standard deviation time of febrile neutropenia was day 7 ± 2 days (range: day -3 to day +13). The most common bloodstream isolate was Escherichia coli (n = 9) followed by Staphylococcus epidermidis (n = 5). One patient developed Fusarium infection. In central line infections, S. epidermidis was the most common organism (n = 8). In 2 patients with central venous catheters, Candida albicans was the isolate. Transplant-related mortality from sepsis occurred in 9.2%. CONCLUSION: E.coli was mainly responsible for BSI, while gram-positive organisms dominated catheter-related febrile episodes. Transplant-related mortality due to sepsis was 9%.

Outcome of adult patients with acute lymphoblastic leukaemia receiving the MRC UKALL XII protocol: a tertiary care centre experience.

INTRODUCTION: Acute lymphoblastic leukaemia (ALL) is a heterogeneous group of lymphoid neoplasm resulting from the proliferation of malignant lymphoid cells. We aimed to study the outcome of adult patients with ALL receiving the Medical Research Council UKALL XII protocol. METHODS: This was a retrospective study conducted at Aga Khan University Hospital from January 2001 to December 2008. The medical records of all adult patients were reviewed and analysed for clinical, morphological and immunological features at presentation and impact on treatment outcomes. Multivariate analysis and survival studies were performed using Kaplan-Meier statistics. RESULTS: The total number of patients was 54, with a male to female ratio of 3.4:1 and a median age of 28 years. Common presenting symptoms were fever (n is 49) and bleeding (n is 14). 38 patients had haemoglobin less than 10 gms/dl, 21 had white blood cell (WBC) count of 50 × 10E9/L or more, and 35 had lactate dehyrogenase more than 1,000 IU. Morphologically, FAB-L2 was the commonest subtype, with 38 patients with B-ALL and eight with T-ALL. Multivariate analysis showed that age above 30 years, male gender, WBC count above 50 × 10E9/L and T-ALL subtype were independent risk factors for poor survival. 46 (85 percent) patients achieved complete remission. The median survival was 12.3 months. At the end of five years, 16 patients were alive, two were alive with disease and 14 were in complete remission. CONCLUSION: Overall survival and relapse rates in our study were comparable to those reported internationally.

Chronic phase chronic myeloid leukemia: response of imatinib mesylate and significance of Sokal score, age and disease duration in predicting the hematological and cytogenetic response.

OBJECTIVE: To evaluate the response of imatinib mesylate in chronic phase of chronic myeloid leukemia and to observe the significance of Sokal score and various factors which predict the response. METHODS: This was a descriptive, prospective study conducted from May 2001 to September 2006. One hundred and thirty six patients with diagnosis of chronic myeloid leukemia in chronic phase were analyzed. Hematologic and cytogenetic responses were assessed according to defined criteria. RESULTS: The median age at time of diagnosis was 33 years (range, 12-65 years). Among them 86 were males, 50 were females. At the end of study response was analyzed overall and according to Sokal score. At median follow-up of 18 months, 122 patients were evaluable for cytogenetic response. Complete hematologic response was seen 86% while complete and major cytogenetic response was observed in 34.4% and 49.2% cases respectively. Analysis of variables like younger age, disease duration at time of starting imatinib failed to show any significant influence on response to imatinib mesylate, however, response was found to be higher in patients who had low Sokal score at the time of presentation. CONCLUSION: Imatinib mesylate has substantial activity in chronic phase of CML. Low Sokal score at time of presentation predict the higher hematologic as well as cytogenetic response in patients with chronic phase.

Flow cytometric and demographic analysis of t cell acute lymphoblastic leukemia in Pakistani population.

BACKGROUND: This study was carried out to analyze the proportion of T cell acute lymphoblastic leukemia (TALL) among all acute lymphoblastic leukemia (ALL) in Pakistani population and its correlation with the demographic features. Accuracy of cell surface markers used in flow cytometric analysis of the leukemic cells was also determined. METHODS: Data of 209 consecutive cases of acute lymphoblastic leukemia (ALL) presenting between July 1995 and July 2003 was analyzed. Flow cytometry was performed on all ALL cases using the standard protocols. TALL markers included CD3, CD5 and CD7. RESULTS: Proportion of TALL among known ALL Pakistani patients was 17.22%. Mean age of the TALL patients was 17.2 years. Proportion of TALL was higher in adults than in children (21.95% vs. 14.17%). Overall in this study there were more male patients affected by TALL (25/36 or 69.40%) than females (11/36 or 30.60%). The female to male ratio among TALL patients was 1:2.27. However, the proportion (%) of TALL in females was higher than males (18.96% vs. 15.82 %) i, e, 1.2:1. CD7 was found to be the most sensitive among both adults & children. It was positive in 94.4% of the TALL cases. CONCLUSION: Proportion of TALL among ALL in Pakistan is similar to that reported in this region, indicating a candidate association with geographical location and socioeconomic status. The reactivity of markers with TALL. cells was similar to what we expected based upon literature. However, due to some aberrant and cross reactivity displayed by each marker, we strongly recommend a panel approach including B and myeloid markers to ensure a correct diagnosis of TALL.

Frequency of hereditary thrombophilia: an AKUH experience.

OBJECTIVE: To determine the frequency of various causes of hereditary thrombophilia at a referral laboratory and the age and gender distribution. METHODS: This is a descriptive study incorporating a retrospective analysis of requests for thrombophilia screening sent to Clinical laboratory, Aga Khan University Hospital from November 1995 to May 2002. Patients were screened for hereditary causes of thrombophilia including Protein C, Protein S, antithrombin III, Factor V Leiden and homocysteine. Frequency of each disorder; and age and sex distribution was determined. RESULTS: All the patients suspected clinically for thrombophilia were screened. Of the 2825 patients, 70 were diagnosed to have inheritance as a cause of thrombophilia with a frequency of 2.3% for protein C deficiency, 1.4% for protein S deficiency, 1.5% for antithrombin III deficiency, 14.2% for factor V leiden mutation and 2.0% for homocystenemia. CONCLUSION: All the causes of hereditary thrombophilia can be diagnosed by relatively simple laboratory methods, however because of the low frequency of these disorders the screening of general population is not indicated in the absence of clinical symptoms. More prospective studies are required to define the occurrence of these disorders and other causes of thrombosis.

Prevalence of hepatitis C virus in lymphoproliferative disorders.

OBJECTIVE: To study the prevalence of hepatitis C virus in lymphoproliferative disorders. METHODS: A case control prospective study was performed on 143 patients with lymphoproliferative disorders and 29 patients with non-hematological malignancies were taken as controls. All the patients in both groups were analyzed for various risk factors for infection with hepatitis C virus and were tested for the presence of hepatitis C virus antibody (anti HCV), cryoglobulins and rheumatoid factor antibody. Hepatitis C viremia was documented by detection of HCV RNA by polymerase chain reaction. RESULTS: There was no significant difference for risk factors for hepatitis C virus infection in both the groups except for the increase in number of surgical procedures being carried out in the control group. There was no significant difference in the presence of rheumatoid factor antibody in both the groups and cryoglobulins were not positive in any individual. Five percent patients with lymphoproliferative disorders and 3.4% with non-hematological malignancies were positive for anti HCV. HCV RNA was detected in 29.2% cases and 31.0% in controls. CONCLUSION: There was no association between hepatitis C virus infection and lymphoproliferative disorder in our population. However, further studies are required from this region to establish any causal relationship between hepatitis C virus infection and lymphoproliferative disorder.

Polycythemia vera and idiopathic erythrocytosis: comparison of clinical and laboratory parameters.

OBJECTIVE: To evaluate the various clinical and laboratory parameters of Polycythemia vera and idiopathic erythrocytosis in order to differentiate between two entities at the Aga Khan University Hospital. METHODS: Twenty six patients of polycythemia vera and 34 patients of idiopathic erythrocytosis were analyzed with respect to clinical features and laboratory findings. RESULTS: Patients with idiopathic erythrocytosis were males with a mean age of 41 years and no splenomegaly. Patients with polycythemia were older males and females with splenomegaly, red cell count of mor than 6.5 million/cmm, haematocrit 55%, leucocytosis, thrombocytosis and low erythropoietin level. CONCLUSION: Based on the above-mentioned findings, we suggest that polycythemia vera and idiopathic erythrocytosis are separate entities and the diagnosis of these can be made on the basis of clinical and laboratory parameters.

Increased expression of HLA DR2 in acquired aplastic anemia and its impact on response to immunosuppressive therapy.

OBJECTIVE: To study the frequency of HLA DR2 status of patients with aplastic anemia and their response to immunosuppressive therapy at a tertiary care hospital. METHODS: Thirty eight consecutive patients of acquired aplastic anemia were evaluated with respect to demographic features, severity of HLA DR2 status and response outcome to immunosuppressive therapy. RESULTS: The mean age of the patients was 24.6 years + 16.4 with a male to female ratio of 2.8:1. Positivity of HLA DR2 was markedly high in acquired aplastic anemia patients. Twenty four (65%) out of 38 patients as compared to 45 (15%) of 300 healthy controls (p<0.0001) were positive for HLA DR2. Response to immunosuppressive therapy, which included antilymphocyte globulin, cyclosporin and methylprednisolone, was available in sixteen HLA DR2 positive patients and was found satisfactory in 12/16 (75%) patients. CONCLUSION: HLA DR2 was significantly higher in patients with acquired aplastic anemia and favourable response to immunosuppressive therapy was also associated with HLA DR2 positivity.

Hematologic and cytogenetic findings in eleven chronic myelogenous leukemia patients treated with imatinib mesylate at a tertiary care hospital.

OBJECTIVE: To evaluate the response of Imatinib mesylate in patients with myeloid leukemia in chronic accelerated and blast phase. PATIENTS AND METHODS: Eleven patients with established diagnosis of chronic myeloid leukemia were treated with Imatinib mesylate. Adverse events were documented with regular follow ups. Hematological and cytogenetic responses were assessed according to established criteria. Patients with zero percent Philadelphia positive metaphases were labeled as complete cytogenetic response while patients with 1% to 35% Philadelphia positive metaphases were termed as partial responders. RESULTS: Of 11 cases there were 7 males and 4 females with a mean age of 39.5 years and median age 51 years (range 21-69). Male to female ratio was 7:4. Median follow-up was 34 weeks (range 8-78). Four patients were in blast crisis, 1 in accelerated phase and remaining six patients were in chronic phase. All patients achieved hematological response. Cytogenetic response was present in six patients, 3 were responders and the remaining were non responders. Two patients achieved complete cytogenetic response and one patient had partial cytogenetic response. Both patients with complete cytogenetic response relapsed in twelve weeks time. CONCLUSION: Imatinib mesylate is a drug with curative potential and can be used as a first line drug in the management of CML, however at present the cure rate is unknown.

Acute thrombotic thrombocytopenic purpura following doxycycline treatment of Chlamydia pneumoniae infection in a patient with dermatomyositis.

A 48-year-old white female who was suffering from dermatomyositis and Chlamydia pneumoniae infection, developed acute rapidly fatal thrombotic thrombocytopenic purpura (TTP) following treatment with steroids and doxycycline. As a relationship between TTP and the inflammatory myopathies is now probably well established, it is very likely that our patient's TTP became manifest in association with dermatomyositis. Nevertheless, C. pneumoniae infection and doxycycline therapy cannot be excluded entirely as cofactors responsible for triggering her thrombotic microangiopathy.

Outcome of adult acute lymphoblastic leukemia: a single center experience.

OBJECTIVE: To study the outcomes of adult patients with acute lymphoblastic leukemia. SETTING: Tertiary care hospital. STUDY DESIGN: Retrospective analysis. METHODS: Fifty eight adult patients (age >14 years) diagnosed as cases of acute lymphoblastic leukemia were studied with respect to their clinical, morphological and immunopathological features at presentation and their relationship with treatment outcomes. RESULTS: Forty five (77.5%) of the patients belonged to younger age group with male preponderance. The median age was 20 years and mean age was 25.1 years. Male to female ratio was 3:1. Common presenting signs were lymphadenopathy (17.2%), hepatomegaly (32.7%) and splenomegaly (62%). Laboratory features at presentation revealed: hemoglobin > or = 10 gm/dl in 18 (31%), WBC >50 x 10E9 / L in 18 (31%), LDH more than 1000 IU/L in 44 (75.8%) of patients. Morphology revealed that FAB L1 was seen in 21(37.2%) and L2 in 62 (32.7%). Immunophenotyping showed that 26 (61.9%) were early pre-B ALL, 6 (14.2%) were pre-B ALL and T-ALL were 10 (23.8%). Univariate analysis showed age more than 30 years, male gender, total leucocyte count >50 x 10(9)/L and hemoglobin more than 10 gm/dl to be risk factors for poor outcome. Multivariate analysis revealed age more than 30 years, male sex and total leucocyte count > 50 x 10(9)/L are independent risk factors for poor survival. Patients were treated according to the MRCUKX and XII adult protocols. Thirteen (22.4%) patients died during induction therapy secondary to sepsis and progressive disease whereas 42 (72.4%) patients achieved complete remission. Median survival was 18.6 months and 42% patients were alive at 5-years. CONCLUSION: Overall survival and disease free survival were comparable to those reported in literature. However, age more than 30 years, male gender and total leucocyte count >50 x 10(9)/L had an adverse impact on overall survival.

Use of intravenous anti-D in patients with refractory and relapsed immune thrombocytopenic purpura.

OBJECTIVE: To determine the response to i.v. anti-D and its comparison with splenectomy as second line therapy in refractory and relapsed cases of ITP, in the Aga Khan University Hospital, Karachi. METHODS: A total of 23 patients with chronic ITP were treated with either anti-D or splenectomy as second line treatment. The patients were assessed for time to achieve a response to second line treatment, duration of response and adverse events. RESULTS: There were 12 patients in the anti-D group and 11 in the splenectomy group. The mean platelet count at presentation was 9,000/cumm. The mean age was 8.9 years and 13.0 years and the male to female ratio was 1:1 and 1:1.2 in anti-D and splenectomy group respectively. 54.5% of the patient in the anti-D group responded compared to 81.8% in the splenectomy group. Median time to achieve a response was 7 days in the anti-D group and 1 day in the splenectomy group. Mean time to relapse was 87.8 days in the anti-D group and 55.4 days in the splenectomy group. No adverse events were recorded for any of the infusions of anti-D and none of the patients had more than 0.5 gm/dl fall in the hemoglobin level following anti-D infusion. CONCLUSION: It was thus concluded that Anti-D is a relatively safe, convenient and effective therapy for chronic ITP and can be used as a splenectomy sparing agent when treatment is clinically indicated.

Long-term outcomes of acute myeloid leukemia in adults in Pakistan.

OBJECTIVE: To describe the long-term outcomes of Acute Myeloid Leukemia (AML) and to study clinicopathological features at presentation, morphological subtypes and remission rates. METHODS: Demographic information, response to therapy and survival of patients (>14 years of age) admitted between January 1988 to August 1996 with acute myeloid leukaemia was retrieved and analysed. RESULTS: Seventy-four patients were admitted with a diagnosis of AML during the study period. There were 43 males and 31 females. Age ranged between 15 and 70 years with a mean age of 38 years. The most common presenting feature was fever (67.5%) and the morphological subtype according to French-American-British Group (FAB) criteria was M4. Fifty-five patients received treatment and were evaluable for response and outcomes. Thirty-six (65.4%) patients had complete remission. Sixteen (29.1%) died during the first 28 days after starting induction chemotherapy. The median survival was 11 months. Six (11%) patients (4 females, 2 males) are surviving beyond 4 years (long-term survivors). CONCLUSION: Our study suggests that the long-term outcomes of adults with AML are comparable to what has been reported in the literature for patients who do not receive bone marrow transplants.

Epidemiological features of aplastic anaemia in Pakistan.

OBJECTIVE: To complete the data on the demographic features of patients diagnosed to have aplastic anemia at a single institution over a 7.5 years period. METHODS: Demographic information was retrieved from the patients medical records retrospectively as well as prospectively of those patients who presented with features of aplastic anaemia. Their diagnosis was confirmed by performing a complete blood count and bone marrow trephine. RESULTS: One hundred and forty four patients were diagnosed to have aplastic anemia; there were 106 males and 38 females. Their ages ranged from 2 to 75 years, with a median of 17 years, 112 (77.7%) patients were below the age of 30 years. Severe aplastic anemia (SAA) was seen in 74 (51.4%), very severe (VSAA) in 24 (16.7%) and non-severe aplastic anemia (NSAA) in 46 (31.9%) patients. No obvious cause could be established for 74.3%. Thirteen patients admitted using drugs known to cause AA and one was a radiographer (9%). Out of 44 patients tested, 7 (15.9%) were found to have either hepatitis B virus markers or antibody to hepatitis C at the time of diagnosis of AA. However it was difficult to establish a cause and effect relationship with either drugs or viruses. CONCLUSION: Aplastic anaemia is found to occur mostly in young males. The most common type was idiopathic severe aplastic anaemia.