Clinical characteristics, outcome and early induction deaths in patients with acute promyelocytic leukaemia: a five-year experience at a tertiary care centre

<p><b>INTRODUCTION</b>Acute promyelocytic leukaemia (APL) is a distinct clinical and biological subtype of acute myeloid leukaemia. APL is notorious for causing early death during induction therapy, resulting in induction failure. The aim of our study was to report the clinical characteristics, outcome and early induction deaths with regard to patients with APL seen at our hospital.</p><p><b>METHODS</b>This was a retrospective study carried out at Aga Khan University Hospital, Karachi, Pakistan. Patients aged > 15 years diagnosed with APL within the period September 2007-September 2012 were included in the study.</p><p><b>RESULTS</b>Within the study period, 26 patients were diagnosed with APL based on morphology and the detection of t(15;17)(q24.1;q21.1) and promyelocytic leukaemia-retinoic acid receptor alpha (PML-RARA). The male to female ratio was 1:1. The median age of the patients was 41 (range 16-72) years. In all, there were 13 (50.0%) high-risk patients, and early induction death rate was 61.5%. Causes of early induction deaths (n = 16) included haemorrhage in 7 (43.8%) patients, differentiation (ATRA) syndrome in 7 (43.8%) and infection in 2 (12.5%). The survival rate among patients who survived the early period was 70% at 42 months. The relapse rate was 30%.</p><p><b>CONCLUSION</b>Early induction death rate was very high in patients with APL. The most common cause of early induction death in our study was haemorrhage. Outcome among patients with APL was found to be better among those who survived the initial period.</p>

Chromosomal abnormalities in primary myelodysplastic syndrome

To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome [MDS] using conventional karyotyping. Case series. The Clinical Laboratory. The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature [ISCN, 1995] and described as frequency percentage. Out of the 122 cases of MDS, 71 patients had their karyotype done at the time of diagnosis, including 42 males [59.2%] and 29 females [40.8%] with median age of 60 years. Forty one [57.7%] showed normal karyotype and 30 [42.3%] showed clonal karyotypic abnormalities at diagnosis. Out of which 14 [19.7%] had single, 11 [15.5%] had complex and 6 [8.5%] had double cytogenetic abnormalities. The common abnormalities found were: trisomy 8 in 7 cases [9.9%], -7/del [7q] in 3 cases [4.2%], -Y and complex 5q in 2 cases [2.8%] each, complex trisomy 8, del 11q, inversion 9, trisomy 19 and del 20q were found in 1 case [1.4%] each. Other abnormalities were found in 11 cases [15.5%]. Trisomy 8 was the most common disorder/abnormality found in this study population followed by the complex cytogenetics

Therapeutic outcomes of older patients with acute myeloid leukemia

To evaluate the therapeutic outcomes of acute myeloid leukemia [AML] in elderly patients. This study was conducted at the Aga Khan University Hospital, Karachi, Pakistan over 11 years from January 1997 to August 2008. This was a descriptive case series study. We investigated the impact of disease biology and various treatment protocols on the outcome in this population. A total of 55 evaluable patients [>60 years of age] were diagnosed with AML including 34 [61.8%] males and 21 [38.2%] females. The median age was 67 years [range 60-86 years] at the time of presentation. The AML was preceded by myelodysplastic syndrome in 15 [27.2%] patients. High-risk cytogenetics were observed in 3 [5.4%] patients. Forty patients received palliative treatment while only 15 received chemotherapy. Of the last group with primary AML [n=10], there were 2 remitters, one showed resistant disease while 8 had induction death. The overall mean survival was 75.1 days [95% confidence interval: 46.7-103.5 days] in all patients. There was no survival advantage in patients treated with chemotherapy versus those conservatively treated. We found high mortality among aged patients with AML in our setting. Patients receiving chemotherapy were extremely intolerant to toxic drugs and succumbed earlier than patients receiving palliative care only

Copper sulphate toxicity in a young male complicated by methemoglobinemia, rhabdomyolysis and renal failure

Copper sulphate is a compound prepared by the action of sulphuric acid on copper II. Copper sulphate is widely used as fungicide, herbicide and for photography. In a human being, it can lead to anemia. Medical literature is lacking regarding accidental or suicidal poisoning cases of copper sulphate in Pakistan. We present a case of accidental ingestion of copper sulphate resulting in severe acute toxicity, which was successfully managed by intensive supportive measures and Dimercaprol [BAL]

Diagnostic tool for glanzmann's thrombasthenia clinicopthologic spectrum

To platelet aggregometry and describe the clinical spectrum of Glanzmann`s thrombasthenia diagnosed by platelet aggregometry. A case-series. This study was carried out at the clinical laboratories at the Aga Khan University Hospital, Karachi from January 2003 to January 2006. All patients irrespective of age and gender presenting with bleeding symptoms and having normal platelet count were evaluated. Demographic details, relevant clinical history along with results of complete blood count, bleeding time and platelet aggregation studies were retrieved through computerized data base and evaluated for the diagnosis of Glanzmann`s thrombasthenia. During the study period, 50 out of 2317 patients [2.2%] were diagnosed as Glanzmann`s thrombasthenia by platelet aggregometry with male to female ratio of 0.85:1 and median age of 10.2 years [ranging from 3 months to 27 years]. Common symptoms were epistaxis, oral and gingival bleed, bleeding from minor cuts and trauma that were observed in 46% of the patients; while 18%, 8% and 10% of them also complained of bruising, hematuria and bleeding per rectum respectively. Majority i.e. 86% had a bleeding time greater than 10 minutes. All patients had received blood or blood products for their bleeding episodes. Platelet aggregometry is a useful diagnostic modality for the assessment of Glanzmann`s thrombasthenia. The disorder presents with muco-cutanoeus bleeding and was found to be a common cause of bleeding in our setup

Significance of cytogenetic abnormalities in acute myeloid leukaemia

To evaluate the role of karyotype in acute myeloid leukaemia [AML] as a predictor of response to induction chemotherapy. A cross-sectional study was carried out at the department of Pathology and Oncology, Aga Khan University Karachi from January 2003 to January 2005. Newly diagnosed patients with denovo AML admitted to the hospital were included in the study. Diagnosis of AML was based on FAB criteria, immunophenotyping and cytogenetic studies. They were treated according to standard protocols [combination of anthracycline and cytarabine -3+7] and those who had acute promyelocytic leukaemia additionally received all- trans retinoic acid [ATRA]. A total of 56 patients were enrolled, 4 were excluded due to inadequate cytogenetic analysis and the remaining patients entered the study protocol. There were 32 males and 20 females with mean age of 31.3 years [range 9 months to 73 years]. Thirty-five [67.3%] patients had normal karyotype while 17 [32.7%] were found to have cytogenetic abnormalities. Eleven patients did not receive treatment at our hospital. Half of the [51.2%] patients out of remaining 41 achieved complete remission on bone marrow examination after receiving induction chemotherapy. In favourable risk group 3/3 [100%] achieved complete remission [CR] while 15/32 [46.9%] in intermediate risk group and 3/6 [50%] in unfavourable risk group. There was low CR rate in patients with high white cell counts. The frequency of cytogenetic abnormalities in AML and response to induction chemotherapy was low when compared with international data possibly due to the small sample size. However, there was a clear difference in CR rates between favourable and unfavourable risk groups

Freequency of FAB subtypes i acute myeloid leukemia patients at Aga Khan University Hospital Karachi

Acute myeloid leukemia [AML] is a heterogeneous disease. Therefore, various parameters are needed to classify this disease into subtypes, so that specific treatment approaches can be utilized effectively. The commonly used method for diagnosis and classification is based on FAB criteria using morphology and cytochemical stains. For sonic of the categories, imnninophenotyping is necessary. The aim of present study is to determine the frequency of various sub types in acute myeloid leukemia using FAB criteria in our population. This will aid in the correct diagnosis of acute leukemia and hence proper management of the patients. Materials and This is descriptive case control study conducted at Aga Khan University Hospital from January 1999 to December 2000. The total number of subjects was 116 that included both adults and children. The patients were diagnosed on the basis of bone marrow morphology using FAB classification. Cytochemistry was done in all cases, while immunophenotyping was considered only in those cases that were found to be problematic. Among 116 patients, 70 were males and 46 were females with male to female ratio 1.5:1. The age ranged between 6 months to 85 years with a mean age of 32 years. AML-M4 was the predominant French American-British [FAB] subtype [36.2%] followed by M2 [30.25%], M3 [10.4%], M1 [7.7%]. M5a [3.5%], M5b [2.5%] and M6 [0.8%]. Conclusions: The most common FAB subtype observed in our study was Acute myclomonocytic leukemia [M4] which is in accordance with studies reported from Saudia Arabia and a previous study reported from our institution. However, other national and international studies have reported Myeloblastic Leukemia with maturation [M2] as the predominant subtype of AML