Impact of Aberrant Myeloid Antigen Expression on Outcomes of Patients with T-cell Acute Lymphoblastic Leukemia.

OBJECTIVES: To evaluate the impact of myeloid antigen expression on complete remission (CR), event-free survival (EFS), and overall survival (OS) in patients with T-cell acute lymphoblastic leukemia (T-ALL) treated with intensive chemotherapy. METHODS: We retrospectively reviewed consecutive patients diagnosed with T-ALL and treated in Sultan Qaboos University Hospital and Royal Hospital in Oman between 2004 and 2010. The diagnosis of T-ALL was established using French-American-British classification or World Health Organization criteria. Patients were considered having myeloid antigen expression if they expressed CD13, CD33, or both (My+ and My-). RESULTS: Of the 39 patients, 38 were included in the study (25 patients with My- and median age of 18.4 years, 13 patients with My+ and median age of 22.0 years). Median follow-up was 12 months. Thirty-two out of the total cohort were eligible for response-rate assessment. Twenty-nine patients (90.6%) achieved CR with one or two courses of chemotherapy with similar CR rates between the two groups (p = 0.880). Twenty-five percent (5/20) of the patients with My- required two courses of induction, whereas 58.3% (7/12) of My+ required two courses of induction and the difference was statistically significant (p = 0.040). In the multivariable analysis; age, gender, initial white blood cell count, central nervous system disease, and myeloid antigen expression were not statistically significant predictors of CR. The EFS and OS were similar between the My+ and My- groups p = 0.180 and p = 0.440, respectively. CONCLUSIONS: Patients with T-ALL with myeloid antigen expression need more courses of induction; however, rates of CR, EFS, and OS are not different from those without myeloid antigen expression. Larger prospective studies are required to confirm these findings.

Rituximab leads to long remissions in patients with chronic immune thrombocytopenia.

OBJECTIVES: To assess the response rate and duration of response in patients with chronic immune thrombocytopenia (ITP) receiving rituximab. METHODS: We retrospectively analyzed 32 consecutive patients with chronic ITP who were treated in two tertiary centers in Oman. Response assessment was based on the American Society of Hematology criteria. RESULTS: Nineteen patients (59%) had an initial response. However, six of the 19 patients lost their response leaving 13 patients with long-lasting remissions. The median age at diagnosis was 25 years (range 14-58). The median time from diagnosis to rituximab therapy was 21 months. The median follow-up after starting rituximab was 26 months. The overall cumulative response rate was 59% (complete response 44%, partial response 15%) and the median time to respond was 30 days with a response rate of 44% at four weeks. In all responders, the cumulative rate of loss of response was 32% with a median time to lose response of 54 months. CONCLUSIONS: The use of rituximab in ITP achieves high response rate and long remission duration. Our study was limited by the small sample size and further larger prospective studies are recommended.

Management dilemmas in patients with mechanical heart valves and warfarin-induced major bleeding.

Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging. There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleeding as well as the ideal time to restart warfarin therapy safely without recurrence of bleeding and/or thromboembolism. Presently, the treatments available to reverse warfarin-induced bleeding are vitamin K, fresh frozen plasma, prothrombin complex concentrates and recombinant activated factor VIIa. Currently, vitamin K and fresh frozen plasma are the recommended treatments in patients with mechanical heart valves and warfarin-induced major bleeding. The safe use of prothrombin complex concentrates and recombinant activated factor VIIa in patients with mechanical heart valves is controversial and needs well-designed clinical studies. With regard to restarting anticoagulation in patients with warfarin-induced major bleeding and mechanical heart valves, the safe period varies from 7-14 d after the onset of bleeding for patients with intracranial bleed and 48-72 h for patients with extra-cranial bleed. In this review article, we present relevant literature about these controversies and suggest recommendations for management of patients with warfarin-induced bleeding and a mechanical heart valve. Furthermore, there is an urgent need for separate specific guidelines from major associations/ professional societies with regard to mechanical heart valves and warfarin-induced bleeding.

Acquired Pure Red Cell Aplasia caused by Parvovirus B19 Infection following a Renal Transplant.

We report a young Omani male who developed severe and persistent anaemia after a kidney transplantation while being on immunosuppression therapy, standard practice to prevent rejection of the transplanted kidney. His bone marrow aspirate showed the classic morphological changes of pure red cell aplasia (PRCA), induced by parvovirus B19 infection which is the presence of giant proerythroblasts with viral inclusions. The virus was also demonstrated by polymerase chain reaction in the blood along with IgM antibodies to parvovirus B19. He responded dramatically to high dose immunoglobulin with a normalisation of his haemoglobin level in two weeks and remained normal until seven months later. Parvovirus B19 induced PRCA can be cured. This aetiology must be kept in mind especially when a chronic anaemia, refractory to treatment, is accompanied by a reticulocytopenia. The latter reflects the lysis of the proerythroblasts, preventing maturation of the erythroid cells causing anaemia. Early recognition and prompt treatment spares the patient unnecessary exposure to blood transfusions, erythropoietin and renal disease caused by the virus. PRCA secondary to parvovirus B19 infection following kidney transplantation is reported in the literature, but not in the Omani population. To the best of our knowledge, this is the first such report in Oman.

Indicators of Renal Glomerular and Tubular Functions in Patients with Beta-Thalassaemia Major: A cross sectional study at the Royal Hospital, Oman.

OBJECTIVES: There are limited data concerning the assessment of renal function in beta-thalassaemia major, with no study of such involvement in Omani patients. The objective of this study was to establish the pattern of renal glomerular and tubular function using traditional and specific laboratory tests in patients with beta-thalassaemia major. METHODS: This cross-sectional study, from January-July 2008, included 30 patients of the Thalassaemia Clinic at the Royal Hospital, Oman, with transfusion-dependent homozygous beta-thalassaemia major. They included 15 males and 15 females, aged 16-32 years with mean ± standard deviation of 21.23 ± 3.42 years. The medical records were reviewed and renal function states assessed as follows: serum creatinine, estimated glomerular filtration rate (eGFR); urea; phosphate, fractional excretion of filtered sodium (FENa); urine albumin: creatinine index; urine ß2-microglobulin:creatinine index; tubular reabsorption of phosphate (TRP), and tubular maximum phosphate reabsorption (TmP)/GFR. RESULTS: All patients had eGFR >90 ml/min/1.73m(2); serum creatinine <90 µmol/L; serum urea <6.0 mmol/L, and urine albumin:creatinine <2.5 mg/mmol. Only 2 (6.7%) patients had FENa >1% and 3 (10.0%) patients had urine ß2-microglobulin: creatinine >22 µg/mmol. All patients had TRP >0.85, of whom seven (23.3%) patients had values within the range of 0.85-0.95 and 23 (76.7%) had values >0.95. Also, all patients had TmP/GFR >1.0 mmol/L, of whom only one (3.3%) patient had TmP/GFR of 1.0-1.5, and 29 (96.7%) patients had TmP/GFR >1.5 mmol/L. Finally, 24 (80%) patients had serum phosphate >1.4 mmol/L. Linear regression revealed a highly significant correlation between serum phosphate and TmP/GFR (r = 0.904, P < 0.001). CONCLUSION: Renal function, glomerular and tubular, appears to be well preserved in beta-thalassaemia major. Almost all renal function indicators were within the recommended ranges. Raised TmP/GFR and TRP were noted in the majority of patients, reflecting an up-trend in serum phosphate and therefore increasing renal phosphate reabsorption.

Hairy Cell Leukaemia in Oman: Four cases.

Hairy cell leukaemia (HCL) is a rare, clonal, chronic lymphoproliferative disorder commonly seen in males in the middle years of life. Pancytopaenia with moderate to massive splenomegaly is the most common clinical presentation. Diagnosis is made on detecting the lymphocytes with abundant cytoplasm which spread into hair-like processes on peripheral blood and bone marrow smears, thus giving the name, "hairy cell leukaemia". The bone marrow aspirate is frequently a dry tap. The trephine biopsy has the characteristic features of a honey comb appearance and flow cytometry is typically CD103, CD25, FMC7, CD11c, gamma or kappa light chain positive with the classic B lymphocyte markers CD19, CD20, CD79a. Purine analogues followed by granulocyte-colony stimulating factor (G-CSF) to manage the febrile neutropenia is currently the treatment of choice. A 10 year disease free survival is recorded with these management strategies. Experimental use of anti CD20 and CD22 has also shown promising results in the treatment of this disease. We report four cases of HCL diagnosed in a span of two years at the Royal Hospital, Muscat, Oman.

Prevalence of endocrinopathies in patients with Beta-thalassaemia major - a cross-sectional study in oman.

BACKGROUND: Beta-thalassaemia major is a common medical problem worldwide. There is little data dealing with the nature and prevalence of different endocrine disorders in this disease in the Sultanate of Oman. OBJECTIVES: To establish the prevalence and times of occurrence of endocrine disorders in patients with beta-thalassaemia major. METHODS: This cross-sectional study was conducted during Jan-Jul 2008 and dealt with 30 Omani patients with transfusion-dependent homozygous beta-thalassaemia major who were consulting Thalassaemia Clinic, Royal Hospital. They included 15 males and 15 females, aged 16 to 32 years with median of 21 years and mean ± SD of 21.23 ± 3.42 years. The medical records of these patients were reviewed and their endocrine functions were assessed. This assessment included pituitary and gonadal function, thyroid function, bone profile (including Parathyroid Hormone), morning cortisol and fasting glucose. These profiles were reviewed to exclude hypogonadism, hypothyroidism, hypoparathyroidism, hypoadrenalism or diabetes mellitus. RESULTS: Hypogonadism was reported in 22 (73.3%) patients (13 female, 9 male). Low levels of Follicle-Stimulating Hormone (FSH) and low Luteinizing Hormone (LH) with low estradiol (in females) or testosterone (in males) was noted in 15 (50.0%) patients (7 female, 8 male). Normal (but inappropriately low) levels of FSH and LH with low estradiol (in females) or testosterone (in males) was noted in 7 (23.3%) patients (6 female, 1 male). Primary hypothyroidism was present in only 1 (3.3%) patient (female) who Hypoparathyroidism was found in 3 (10.0%) patients (2 female, 1 male). Diabetes mellitus with high fasting glucose was noted in 8 (26.7%) patients (2 female, 6 male). Morning cortisol levels for all patients were within the reference range with no suspicion of hypoadrenal cortical function. Eight (26.7%) patients had no endocrine disorder, 12 (40.0%) patients had one disorder, 8 (26.7%) patients had 2 disorders, and 2 (6.7%) patients had 3 endocrine disorders. There was no significant difference (p>0.050) in mean serum ferritin in thalassaemics with or without endocrinopathy, regardless of the number of endocrinopathy. CONCLUSION: There is high prevalence of endocrine disorders among Omani beta-thalassaemic adult patients. This signifies the importance of awareness for their development and monitoring for early detection and replacement therapy. No relationship between serum ferritin and development of endocrinopathy was noted.