Cytogenetic profile of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan.

Objective: To determine the frequencies of different cytogenetic abnormalities in patients of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan. Methods: It was descriptive cross-sectional study conducted in Hematology Department of a Tertiary care referral institute from June 2015 to July 2017. All newly diagnosed cases of Acute Leukemia were analyzed. Cytogenetic analysis was performed on bone marrow aspirate samples using Giemsa-trypsin banding technique. Karyotypes were identified and interpreted according to ISCN criteria. Results: A total of 355 newly diagnosed patients of Acute Leukemia were analyzed. Out of these, 180 patients had AML and 175 had ALL. In Acute Myeloid Leukemia chromosomal abnormalities were detected in 28.2 % cases. Of these the common ones included t(8;21),t(15;17),+8, Inversion 16 and Monosomy 7. Other abnormalities included Complex karyotype, Down's syndrome related AML, Hyperdiploidy, del 16q,-8,+Y and t(3p;17q)del 10. In Acute Lymphoblastic Leukemia chromosomal abnormalities were detected in 40% cases. Common ones included Hyperdiploidy, Tetraploidy and t(9;22). Other abnormalities included t(1;19) and t(2;8)t(8;14). Conclusion: Cytogenetically favorable abnormalities are commonest occurring chromosomal defects in both Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia in Northern Pakistan, i.e., t(8;21) in AML and Hyperdiploidy in ALL.

Different Translocations of Multiple Myeloma on Fluorescent In Situ Hybridization (FISH) with Clinical Correlation.

OBJECTIVE: To evaluate the association of chromosomal translocations in multiple myeloma (MM) detected by Fluorescent In Situ Hybridization (FISH) and its clinical characteristics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan, from February to August 2022. METHODOLOGY: A total of 40 cases of MM were included. All cases were diagnosed using international myeloma working group (IMWG) criteria. Clinical presentations like bone pain, backache, fatigue, pallor, and weight loss were noted. The workup for myeloma-defining events was done. FISH analysis was done for t (4;14), t (11,14), t (14;16), t (14;20), and del 17p. Data were analysed using the chi-square test. A p-value ≤0.05 was considered statistically significant. RESULTS: Out of 40 patients, 8 (20%) were females and 32 (80%) were males. The highest frequency of cases were noted among males in the age group >60 years and females in the age group 40-60 years. FISH for t (4;14) was positive in 22 (55%) patients, for t (11;14) was positive in 4 (10%) patients, for t (14;16) was positive in 3 (7.5%) patients, and for t (14;20) was positive in 3 (7.5%) patients, while for del17p was positive in 8 (20%) patients. Cases with t (4;14), t (11;14), and t (14;20) had bone pain, fatigue, and backache as the most common presentations. Among the various parameters studied, lytic lesions, beta-2 microglobulin, spike protein, deranged haemoglobin, TLC, ESR, albumin, and creatinine were significant risk factors in patients who were tested positive for various mutations. CONCLUSION: The FISH technique has brought an immense uprising in the genetic analysis of MM. Among translocations, t (4;14) and del17p are associated with poor clinical outcomes and prognosis. If the diagnosis of MM is delayed, then an increase in morbidity and mortality can occur. KEY WORDS: Multiple myeloma, FISH, Translocations.

Cytogenetic Profile Of Acute Lymphoblastic Leukaemia Patients And Its Association With Induction Remission Status.

Background: Acute lymphoblastic leukaemia is characterized by the presence of more than or equal to 20% lymphoblast (early lymphoid precursors) in peripheral blood and/or in bone marrow. Lymphoblast can infiltrate different organs and clinically patients can present with fatigue, pallor, fever, bone pain, bleeding or bruises and lymphadenopathy. ALL is the most common type of malignancy in children. To determine the cytogenetic abnormalities in patients of Acute Lymphoblastic Leukaemia as a predictor of response to induction chemotherapy. It was a descriptive cross-sectional study. Methods: This study was conducted at the Armed Forces Institute of Pathology, Rawalpindi over a period of six months from June to November 2019. Bone marrow and peripheral blood samples of newly diagnosed 80 patients of all the age groups and either gender, who received one month treatment for ALL,were analyzed for cytogenetic study. Patients who were previously diagnosed with ALL, who presented with relapse and those who required induction treatment outside the trial hospital were excluded. UK ALL 2011 treatment protocol was adopted for patients up to 25 years old and for patients above 25years old UK ALL 2014 treatment protocol as induction chemotherapy was adopted. Evaluation for remission was carried out at the termination of initial induction chemotherapy on day 29 of treatment. Results: A total of 80 patients were enrolled in the study, comprising 36 (45%) females & 44 (55%) males. The median age of paediatric patients was 5years (<19 years) who were 56/80 (70%) in number whereas the median age of adults was 27 years (>19 years) who constituted 24/80 (30%) of the participants. Cytogenetic of 51 (63.75%) patients revealed hyperdiploidy (chromosome number 51-66) whereas 29(36.25%) of the participants had miscellaneous mutations [(Hypodiploidy, t (9; 22), t (1; 19) and t (12; 21)]. On immunophenotyping 51/80 (63.7%) of the leukemias were of B cell origin and 29 (36.25%) of T-cell origin. Conclusion: Patients with hyperdiploidy, t (12;21) ETV6/RUNX1 and t(1;19)TCF3/PBX1 had better prognosis and higher remission rate compared to those with the other mutations like t(9;22)Ph+ and hypodiploid which were associated with poor prognosis. Association of gender with remission was not statistically significant.

Clinico-Haematologic Parameters And Assessment Of Post-Induction Status In Acute Lymphoblastic Leukaemia.

BACKGROUND: Acute Leukaemia is a malignant disorder characterized by an abnormal proliferation of immature cells, called blasts. Classically, acute leukaemia is classified into acute myeloid leukaemia and acute lymphoblastic leukaemia depending on the lineage of the immature cells. Objective of the study was to evaluate the clinical presentations, analyze the haematologic parameters at time of diagnosis and assess the post-induction status in newly diagnosed ALL patients. This cross-sectional study was conducted in the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi from June to November 2019. METHODS: A total of 55 newly diagnosed ALL patients were recruited including children, adults and elderly. Detailed medical history and physical findings were noted. Haematologic parameters were documented. Each patient was treated as per standard protocol and remission induction status was determined on day 29 of treatment. RESULTS: The median age of the study cohort of 55 newly diagnosed ALL patients was 8.5 years. Males were 37 (67.3%) and females were 18 (32.7%) with a male to female ratio of 2:1. Paediatric group included 31 (56.4%) patients. Nine (16.4%) patients were in the adult group and 15 (27.3%) in the elderly age group. The time from onset of symptoms to diagnosis of acute lymphoblastic leukaemia was 98.87±79.21 days. Fever was the most common symptom but body aches were common among paediatric group while pallor was the most common sign. Mean WBC was 29.1±27.9 x109/l, Hb was 8.1±2.9 g/dl and platelet count was 60±41.8 x109/l B-acute lymphoblastic leukaemia was more common than T-acute lymphoblastic leukaemia. A total of 52 patients were assessed on day 29 to evaluate for post-induction remission status. The remission rate of our cohort of patients was 82.7%. CONCLUSIONS: Most of the patients were in paediatric age group and remission rate was better in this age group compared to elderly population. B-ALL was associated with good response to induction chemotherapy while patients with BCR-ABL1 gene rearrangement did not respond well to treatment. Identification of prognostic features at diagnosis will further help our clinicians to predict outcomes of the disease.

Clinico-Haematologic association and prognostic relevance of NPM1 and FLT3-ITD mutations in acute Myeloid Leukaemia.

BACKGROUND & OBJECTIVES: Molecular genetic abnormalities have a significant role not only in diagnosis but also in determining the clinical course and prognosis. Nucleophosmin-1 (NPM-1) is associated with good prognosis while internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) confers a poor prognosis. Knowledge of the status of these mutations in AML patients not only guides treatment decisions but also helps in predicting response to frontline induction and consolidation chemotherapy as well as the risk of relapse and overall survival. Our objectives were to determine the prevalence, clinico-haematological features and immunophenotypic characteristics of AML patients with FLT3-ITD and NPM1 mutation and to evaluate the response to induction therapy (CR) and disease free survival (DFS) in this cohort of patients. METHODS: Patients diagnosed as AML from March 2015 to March 2017 at Armed Forces Institute of Pathology Rawalpindi were included in the study. Clinico-haematologic and immunophenotypic parameters were noted and molecular analysis for FLT3-ITD and NPM1 mutation was performed. Any correlation with cytogenetics or other molecular markers was also studied. Response to standard induction chemotherapy and disease-free survival were assessed. RESULTS: A total of 108 cases of AML were analyzed. Median age was 35 years and 64.8% were males. The median age of the study group was 35 years. Of these, 70 (64.8%) were males while 38 (35.2%) were females. Twenty-nine (26.9%) patients were NPM1 positive, twelve (11.1%) were FLT3-ITD positive while eight (7.4%) were positive for both mutations. Patients with NPM1 mutations were associated with female gender, higher haemoglobin level and platelet counts while those with FLT3-ITD mutations were predominantly seen in male patients and had significantly higher WBC counts, bone marrow blasts, biopsy cellularity and LDH levels. CR rates of NPM1 positive, FLT3-ITD positive and both mutation positive groups were 72%, 60% and 71%, respectively. The median disease-free survival was significantly lower in the FLT3-ITD positive group (7.1 months) as compared to the NPM1 positive group (16.1 months). The median disease-free survival was 12 months and 11.9 months in the NPM1 positive/FLT3-ITD positive and the NPM1 negative/FLT3-ITD negative groups, respectively. CONCLUSION: AML patients harbouring NPM1 and FLT3-ITD mutations have distinct clinical and haematological characteristics. NPM1 mutations have a better CR and DFS as compared to FLT3-ITD group.

Clinicohematological parameters and outcomes in a cohort of chronic lymphocytic leukemia patients with Deletion 17p from Pakistan.

BACKGROUND: Chronic lymphocytic leukemia (CLL) exhibits profound heterogeneity in its clinical course. Its clinicohematological and cytogenetic features play a significant role in determining the clinical course and in predicting the treatment response and prognosis. In this context, 17p deletion is known to predict a poor prognosis, as these cases are refractory to conventional therapy. This study aimed to evaluate the clinicohematological characteristics, outcomes, and prognostic factors among CLL patients with and without del 17p in Pakistan. METHODS: This prospective observational study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (Rawalpindi, Pakistan) between January 2013 and December 2017. Patients were diagnosed based on the International Workshop on Chronic Lymphocytic Leukaemia IWCLL criteria, their clinicohematological parameters were recorded, and cytogenetic analyses were performed. The time from diagnosis to treatment and the 2-year overall survival rate were also evaluated. RESULTS: We evaluated 130 CLL cases, including 24 patients (18.5%) with del 17p, who included 18 men (75%) and 6 women (25%). The median age was 68 years. Binet stage C was detected at the presentation in 16 patients (67%). Treatment was administered to 14 patients (70%) at a median interval of 11 months (range, 0-28 mo) after diagnosis. The overall response rate was 64.3%, the median event-free survival was 9 months (range, 1-23 mo), and the 2-year overall survival rate was 65%. CONCLUSION: Del 17p is relatively common in Pakistan, and patients harboring this deletion had poor treatment response and survival outcomes.

Thiamine Responsive Megaloblastic Anaemia, Diabetes Mellitus and Sensorineural Hearing Loss in a Child.

Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an autosomal recessive inherited disorder characterised by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. We report a case of 2-year-old girl whose anemia improved following administration of thiamine. She came with the history of persistent anaemia for the last one year. Anaemia was not responding to iron, vitamin B12, and folate replacement therapy. The bone marrow aspiration revealed hypercellular marrow with megaloblastic changes and more than 15% ring sideroblasts. The hearing assessment revealed sensorineural hearing loss. Blood sugar random and HBA1c was raised. Final diagnosis of TRMA was made. She was started on thiamine 100 mg OD, with normal routine balanced diet. She responded very well to thiamine. Her haemoglobin improved and blood sugar fasting came down in normal range. This case report sensitises the early diagnosis, and treatment with thiamine in children presenting with anemia, diabetes and deafness.

Myelodysplastic Syndrome in Pakistan: Clinicohematological Characteristics, Cytogenetic Profile, and Risk Stratification.

OBJECTIVE: Myelodysplastic syndrome (MDS) is a group of bone marrow diseases that not only have variable morphological presentation and heterogeneous clinical courses but also have a wide range of cytogenetic abnormalities. Clinicohematological parameters have a significant role in diagnosis and along with identification of cytogenetic abnormalities are important for prognostic scoring and risk stratification of patients to plan management and make treatment decisions. This study aimed to determine the clinicohematological characteristics, cytogenetic abnormalities, and risk stratification of newly diagnosed de novo MDS patients. MATERIALS AND METHODS: This cross-sectional study was conducted in the Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi, from January 2013 to January 2017. Patients were diagnosed on the basis of World Health Organization criteria for MDS, clinicohematological parameters were noted, and cytogenetic analysis was performed. Risk stratification was done using the Revised International Prognostic Scoring System. RESULTS: A total of 178 cases of MDS were analyzed, including 119 males (66.9%) and 59 females (33.1%). The median age was 58 years. The most common presenting feature was anemia in 162 (91%) of the patients. MDS with multilineage dysplasia was the most common diagnosis, seen in 103 (57.9%) patients. A normal karyotype was seen in 95 (53.4%), while 83 (46.6%) showed clonal karyotypic abnormalities at diagnosis. Of these, the common abnormalities found were trisomy 8, complex karyotype, and del 5q. Risk stratification revealed low-risk disease in 73 (41%) patients. CONCLUSION: Cytogenetic analysis showed the normal karyotype to be the most common while risk stratification revealed a predominance of low-risk disease at the time of presentation.

Delta-Beta Thalassaemia in a Pathan Family.

Delta-beta-thalassaemia (δß-thalassaemia) is a rare type of thalassaemia which mostly results from deletion of δ and ß genes with preservation of γ genes. δß-thalassaemia is classified into (δß)+ and (δß)0 types. The (δß)0-thalassemia is further divided into GγAγ(δß)0-thalassaemia and Gγ(Aγδß)0-thalassaemia. In heterozygous state, (δß)0mutations give rise to phenotype resembling ß-thalassaemia trait but with raised Hb-F, ranging from 5 to 20%, without a rise in Hb-A2. In homozygotes, the clinical picture is usually that of thalassaemia intermedia and the patients have 100% Hb-F. Workup of a 1-year child suffering from pallor, chronic ill health, and splenomegaly referred to our laboratory with the suspicion of ß-thalassaemia, ultimately resulted in a diagnosis on polymerase chain reaction as having homozygous inversion/deletion Gγ(Aγδß)0-thalassaemia. Her family members were also investigated.

Frequency of Gγ-globin promoter -158 (C>T) XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia.

BACKGROUND: Response to hydroxyurea therapy in homozygous or compound heterozygous beta thalassaemia (BT) has been reported as more favourable in the presence of XmnI polymorphism. The prevalence of XmnI polymorphism may vary with BT phenotypes and genotypes, and differs geographically in distribution. Prevalence of XmnI polymorphism is not known in northern Pakistan. OBJECTIVE: To determine the frequency of Gγ-globin promoter -158 (C>T) XmnI polymorphism (XmnI polymorphism) in patients with homozygous or compound heterozygous beta thalassaemia. MATERIALS: Polymerase chain reaction (PCR) for common beta thalassaemia mutations and Gγ-globin promoter -158 (C>T) XmnI polymorphism was performed on 107 blood samples of transfusion dependent beta thalassaemia (BT) patients in Pakistan. One hundred samples of unrelated BT traits and 94 samples of healthy subjects as controls were also analysed for BT mutations and XmnI polymorphism. RESULTS: Out of 301 DNA samples, XmnI polymorphism was detected in 71(24%); in normal controls, XmnI polymorphism was detected in 34/94 (36%) subjects; while in homozygous/compound heterozygous BT, it was detected in 14/107(13%) patients (Fisher's exact test, p=.0002). In heterozygous BT group, XmnI polymorphism was detected in 23/100 subjects (Fisher's exact test, p=.03 with normal controls, and p=.049 with homozygous/compound heterozygous BT). The most common BT genotype was Frame Shift (Fr) 8-9/Fr 8-9, and none of the patients with this genotype had XmnI polymorphism. The second most common genotype was IVSI-5/IVSI-5; 4/26 (15%). Cases with this genotype had XmnI polymorphism. CONCLUSION: XmnI polymorphism in homozygous/compound heterozygous BT group is 13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI-5.

Anaesthetic risks in children with obstructive sleep apnea syndrome undergoing adenotonsillectomy.

OBJECTIVE: To determine the frequency of anaesthetic risks in children having Obstructive Sleep Apnea Syndrome (OSAS), undergoing adenotonsillectomy. STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Department of Anaesthesiology, Armed Forces Hospital, Najran, Saudi Arabia from November 2006 to January 2008. METHODOLOGY: The study was carried out in 60 children scheduled to undergo adenotonsillectomy and divided into two equal groups of 30 each. Group-1 had obstructive sleep apnoea syndrome and group-2 had children without it. Both groups were given a standard general anaesthesia and frequency and rate of complications and medical interventions taken in such children were studied. P-value and odds ratio were determined. RESULTS: The age ranged from 3 to 10 years. The frequency of difficult intubation was higher in the group-1 than in the control group (16.6 vs. 3.3%, odds ratio 5.8). At the time of induction of anaesthesia desaturation was higher in group-1 (33.3 vs. 6.6%, p=0.021, odds ratio 7). At the time of extubation, desaturation was significantly higher in group-1 (43.3 vs. 6.6%, p=0.002, odds ratio 10.70). The complications at extubation, for example cough, laryngospasm and postoperative nausea and vomiting were higher in group-1 but not statistically significant. In the postanaesthesia care unit, the frequency of complications and medical interventions were also higher in group-1. More patients of group-1 required oxygen (63.3 vs. 10%, p < 0.001, odds ratio 15.54) and insertion of an oropharyngeal airway (20% vs. nil, p=0.023) respectively. CONCLUSION: Children with OSAS, operated for adenotonsillectomy, are at significant risk of certain life-threatening perioperative anaesthetic complications. These results may be used as a guideline for safe and successful anaesthetic management of these children.

Graft versus host disease in allogeneic stem cell transplantation--3 1/2 years experience.

OBJECTIVE: To evaluate the frequency and outcome of graft versus host disease after allogeneic stem cell transplant in haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from July 2001 to December 2004. METHODS: Eighty-six patients with various haematological disorders namely aplastic anaemia (n=32), b-Thalassaemia (n=25), CML (n=22), ALL (n=3), AML (n=1) Fanconi's anaemia (n=2), and Gaucher's disease (n=1), underwent allogeneic stem cell transplantation. All patients received cyclosoprin, prednisolone and short course of methotrexate as GvHD prophylaxis. The patients who developed acute GvHD > grade-II or chronic extensive GvHD received steroids at a starting dose of 2 mg/kg body weight along with gradual increase in cyclosporine dosage (max dose 12.5 mg/kg). RESULTS: The overall incidence of acute GvHD grade-II to IV was 44.2% (n=38/86) where as the incidence of chronic extensive GvHD was 14% (n=12/86). Acute GvHD was 68% (n=17/25) in beta-Thalassaemia, 50% (n=11/22) in CML, 50% (n=2/4) in Acute Leukaemias and 25% (n=8/32) in Aplastic Anaemia. Chronic GvHD was 25% (n=1/4) in Acute Leukaemias, 18.8% (n=6/32) in Aplastic Anaemia, 18.2% (n=4/22) in CML and 4% (n=1/25) in beta-Thalassaemia. The overall survival in acute GvHD was 84.2% (n=32) where as the overall survival in chronic GvHD was 50% (n=6). The overall mortality in acute GvHD was 15.8% (n=6) and 50% in chronic GvHD (n=6). CONCLUSION: The morbidity and mortality due to severe acute and chronic GvHD remains high despite standard prophylaxis against GvHD. New strategies are needed to prevent and treat GvHD.

Allogeneic stem cell transplantation in chronic myeloid leukaemia--2 1/2 year experience.

OBJECTIVE: To evaluate out come of allogeneic Stem Cell Transplantation (SCT) in chronic myeloid leukaemia (CMC) at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from April 2002 to October 2004. METHODS: Twenty-two patients with CML underwent allogeneic SCT from HLA matched siblings. Patients were divided into standard (n=14) and high-risk (n=8) groups. Patients were subjected to conditioning regimens consisting of Busulphan and Cyclophosphamide. Cyclosporin, Prednisolone and Methotrexate were given for GvHD prophylaxis. All donors were subjected to PBSC harvest after G-CSF therapy for five days. All received G-CSF from Day+5 until ANC >0.5 x 10(9)/l. RESULTS: The median age of the patients was 29 years (range 7-53 years) with a male to female ratio of 6.3:1. Engraftment was achieved in all patients. Median time to achieve neutrophil (ANC 0.5 x 10(9)/l) and platelet (20 x 10(9)/l) recovery was 13 days and 12 days respectively. Median stay in hospital was 18 days. Acute GvHD (Grade-II-IV) was observed in eleven patients (50%) while chronic GvHD was seen in four patients (18%). One patient relapsed 8 months post transplant. Two patients (9%) developed Veno-occlusive disease (VOD) liver. One patient had haemorrhagic cystitis. Four patients (18%) had post transplant infectious complications, which included pseudomonas septicemia, aspergillosis, tuberculous pleural effusion and herpes zoster. Overall mortality was 22.7% (n=5). The major causes of mortality were VOD liver, GvHD grade IV, Pseudomonas septicaemia and aspergillosis. Overall survival was 77.2% (n=17) and disease free survival was (n=16) 72.7%. Follow up ranges were from 23 to 828 days (median 212 days). CONCLUSION: The preliminary results of SCT in this small series of patients with CML are very encouraging. To improve the long-term survival it is imperative that patients are transplanted early after diagnosis and conditioning regimens are selected carefully.

FLAG-IDA in the treatment of refractory/relapsed acute leukaemias: single centre study.

OBJECTIVE: To evaluate the efficacy and toxicity profile of the combination of fludarabine, high dose cytarabine, idarubicin, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a study is being conducted at Armed Forces Bone Marrow Transplant Centre (AFBMTC) Rawalpindi since January 2003. Data up to June 2004 (early report) is being presented. METHODS: Twelve Patients with refractory/relapsed (Ref/Rel) acute leukaemia (AL) were treated with fludarabine 30 mg/m2 and cytosine arabinoside (AraC) Arac 2 g/m2 for 5 days, idarubicin 10 mg/m2 for 3 days, and granulocyte colony stimulating factor G-CSF 5 micro g/kg from day 0 till neutrophil recovery (ANC > 1.0 x 10(9)/1). Response was evaluated by bone marrow examination on day 20-post chemotherapy. RESULTS: Patients included were refractory acute lymphoblastic leukaemia (ALL) (n=2), relapsed ALL (n = 3), refractory acute myeloid leukaemia (AML) (n = 3), secondary AML (n=2) relapsed AML (n = 1) and acute undifferentiated leukaemia (AUL) (n = 1). Complete remission (CR) was achieved in 8 (66.6%) patients. Three (25%) patients died of post chemotherapy complications and one patient failed to achieve remission. Out of 8 patients who achieved CR, 4 underwent allogeneic bone marrow transfusion (BMT), 1 is being evaluated for the same, 1 received idorubicin, AraC and etopuside (ICE) and high dose AraC, 1 did not receive further chemotherapy and 1 relapsed two months after remission. Seven patients are still in CR after a median follow up of 8 months (range 3-18). Major complications encountered were diarrhoea, mucositis, toxic ileus, transient hepatic toxicity, fungal and bacterial infections. CONCLUSION: In our experience, FLAG-IDA is well tolerated and effective regimen in relapsed/refractory acute leukaemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.

Posttransplant Guillain Barre Syndrome.

This case report describes a patient with severe aplastic anaemia, who developed Guillain Barre Syndrome (GBS) 10 weeks after allogeneic haematopoietic stem cell transplantation (HSCT) from HLA-matched sibling-younger sister. GBS was preceded by pneumonia, herpes labialis and oral candidiasis a week earlier. Treatment with ventilatory management, intravenous human immunoglobulin (IVIg) and antimicrobials resulted in smooth recovery in thirty-one days.

Genus and species-specific IgG and IgM antibodies for pulmonary tuberculosis.

OBJECTIVE: To evaluate three different enzyme immunoassays for serological diagnosis of pulmonary tuberculosis and to compare their diagnostic accuracy in different combinations. DESIGN: A non-interventional comparative study. PLACE AND DURATION OF STUDY: The study was carried out at the Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi between April and September 2001. SUBJECTS AND METHODS: Sera from patients suffering from pulmonary tuberculosis (n=94) with sputum positive for acid fast bacilli (AFB) and sera from control group of healthy individuals (n=90) with sputum negative for AFB were tested by Pathozyme-Myco G EIA, Pathozyme-TB Complex Plus EIA and Pathozyme Myco M EIA kits for the genus-specific IgG and IgM, and the species-specific IgG antibodies against antigens of Mycobacterium tuberculosis. RESULTS: The detection of IgG against genus-specific antigens by Pathozyme-Myco G had a sensitivity of 46% and a specificity of 93%, of IgG against species-specific antigens by Pathozyme-TB Complex Plus had a sensitivity of 64% and specificity of 97% and of IgM against genus-specific antigens by Pathozyme Myco M had a sensitivity of 67% and specificity of 98%. When the results of these immunoassays were evaluated in combination, their sensitivity improved. Combination of genus-specific IgM and species-specific IgG yielded best results with a sensitivity of 87% and specificity of 93%. CONCLUSION: The sensitivity of serological diagnosis of tuberculosis is low, but it can be increased by utilizing a combination of several antigens.