Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients

Busulfan [Bu]-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2 mg/kg/day [FBD] given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring [TDM] of Bu. We compared the Bu dose given using TDM with the FBD of 3.2 mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15 years [range 2-55 years] with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39 mg/day with a statistically significant difference [p < 0.001] even after adjusting for the weight [median total FBD of 349 mg, median TDM dose of 494 mg, p < 0.0001]. Age and underlying condition [malignant vs. nonmalignant] were the main factors affecting Bu clearance [p < 0.001 and p < 0.07, respectively]. TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture

First cytogenetic profile of Omani patients with de novo myelodysplastic syndromes - Comparison with data from Asia, Africa, Europe and North and South America

Clonal cytogenetic abnormalities have been reported among 30-80% of patients with myelodysplastic syndromes [MDS]; however, 20-70% of patients with MDS show a normal karyotype that may nevertheless harbour a cryptic genetic alteration. Earlier reports have suggested that the distribution of specific chromosomal aberrations varies among Western and Asian countries, with geographical and ethnic differences in the frequency of specific chromosomal aberrations. This article compared the cytogenetic data of 36 adult Omani patients with MDS to previously reported data from other populations. Differences were noted between the percentages of clonal aberrations and the median age of Omani subjects at presentation in comparison to individuals of different ethnicities and from various geographical locations. To the best of the authors' knowledge, this is the first report to describe the cytogenetic data of patients with MDS from Oman

Unusual indolent course of a chronic active epstein-barr virus-associated natural killer cell lymphoproliferative disorder

Natural killer [NK] cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus [EBV] plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement. A polymerase chain reaction [PCR] test revealed a high EBV viral load in the peripheral blood cells. The patient received a course of piperacillin-tazobactam for Klebsiella pneumoniae, but no active treatment for the lymphoproliferative disorder. However, his lymphocyte count, serum lactate dehydrogenase and liver enzymes dropped spontaneously. In addition, EBV PCR copies fluctuated and then decreased significantly. He remained clinically asymptomatic over the following four years

Relapse of multiple myeloma presenting as lower lip numbness

Multiple myeloma [MM] is an uncommon malignancy characterised by the proliferation of clonal plasma cells. There are few published reports describing the extramedullary presentation of MM manifesting primarily in the head and neck region. In addition, the occurrence of an isolated relapse of MM in these sites is exceedingly rare. We report a 56-year-old female who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2010 with sudden-onset numbness of the lower lip. She had a history of MM in remission following chemotherapy and a bone marrow transplant. Clinical and radiographic examinations were indicative of a possible relapse of MM, which was subsequently confirmed by bone marrow aspiration and histopathological evaluation. This unique case highlights the unusual site of relapse of a haematolymphoid malignancy

Rituximab leads to long remissions in patients with chronic immune thrombocytopenia

To assess the response rate and duration of response in patients with chronic immune thrombocytopenia [ITP] receiving rituximab. 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. 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. 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

Biclonal gammopathy in chronic lymphocytic leukemia: case report and review of the literature

Monoclonal gammopathies are frequently seen in B-cell malignancies. Monoclonal proteins are seen in a significant proportion of patients with chronic lymphocytic leukemia [CLL], which is a clonal disorder of mature B cells. The use of more sensitive laboratory methods has enabled the detection of monoclonal proteins or light chains in the serum and/or urine in the majority of these patients. The presence of some of these monoclonal proteins may explain the different autoimmune phenomena that are associated with this disease. Some reports indicate that the finding of monoclonal proteins has a negative impact on patients' survival. The presence of two different monoclonal proteins [i.e. biclonal gammopathy] is on the other hand rare. Most of the reported cases in the literature are of patients with plasma cell disorders. In this report, we describe a rare occurrence of biclonal gammopathy in a patient with CLL. Serum protein electrophoresis and immunofixation, which were negative at the time of initial diagnosis, showed biclonal immunoglobin A [IgA] kappa and IgA lambda during the course of the disease. The patient's disease showed steady progression, despite multiple treatments. Although this could just be the result of using more sensitive laboratory techniques, biclonal gammopathy in this patient likely reflects the evolution of another clone, which would explain the encountered resistance to therapy. Because of paucity of reports, the impact of biclonal gammopathies in such patients is not known and an effort to collectively report the presentation and outcome of these patients is needed to further understand the pathophysiology and clinical significance of such a finding

Methemoglobinemia in an elderly patient with glucose-6-phosphate dehydrogenase deficiency: a case report

Glucose-6-phosphate dehydrogenase [G6PD] deficiency is an X-linked genetic disorder characterized by low levels of the G6PD enzyme. It is present worldwide but with more prevalence in the Middle East and the Mediterranean areas. We report a case of severe hemolysis due to G6PD deficiency manifesting as methemoglobinemia in a 70 year old Omani male never known to have any previous hemolytic episodes or previously diagnosed of G6PD deficiency.

Non-invasive haemoglobin estimation in patients with thalassaemia major

This study aimed to validate pulse CO-oximetry-based haemoglobin [Hb] estimation in children and adults with thalassaemia major [TM] and to determine the impact of different baseline variables on the accuracy of the estimation. This observational study was conducted over a five-week period from March to April 2012. A total of 108 patients with TM attending the daycare thalassaemia centre of a tertiary care hospital in Muscat, Oman, were enrolled. Spot [Sp] Hb measurements were estimated using a Pronto-7 [Registered Sign] pulse CO-oximetry device [Masimo Corp., Irvine, California, USA]. These were compared to venous samples of Hb using the CELL-DYN Sapphire Hematology Analyzer [Abbott Diagnostics, Abbott Park, Illinois, USA] to determine the reference [Ref] Hb levels. A multivariable linear regression model was used to assess the impact of baseline variables such as age, gender, weight, height, Ref Hb and blood pressure on the Hb estimations. Of the 108 enrolled patients, there were 54 males and 54 females with a mean age of 21.6 years [standard deviation [SD] = 7.3 years; range: 2.5-38 years]. The mean Ref Hb and Sp Hb were 9.4 g/dL [SD - 0.9 g/dL; range: 7.5-12.3 g/dL] and 11.1 g/dL [SD = 1.2 g/dL; range: 7.5-14.7 g/dL], respectively. The coefficient of determination [R[2]] was 21% with a mean difference of 1.7 g/dL [SD = 1.1 g/dL; range: -0.9-4.3 g/dL]. In the multivariable model, the Ref Hb level [P = 0.001] was the only statistically significant predictor. The Pronto-7 [Registered Sign] pulse CO-oximetry device was found to overestimate Hb levels in patients with TM and therefore cannot be recommended. Further larger studies are needed to confirm these results

Multiple myeloma: an update

Multiple myeloma is a rare, largely incurable malignant disease of plasma cells. Patients usually present with hypercalcemia, renal insufficiency, anemia and/or lytic bony lesions along with a monoclonal protein in the serum and/or urine in addition to an increase in the number of clonal plasma cells in the bone marrow. Patients with myeloma live on an average for five to seven years, with their survival dependent on the presence or absence of different prognostic markers. Treatment of younger fit patients is with induction therapy consisting of steroids with one or more novel anti-myeloma agents followed by high dose melphalan and autologous stem cell transplantation, while older and less fit patients are treated with melphalan-based combination chemotherapy. Supportive care is of paramount importance and includes the use of bisphosphonates, prophylactic antibiotics, thrombosis prophylaxis and the use ofhematopoietic growth factors along with the treatment of complications of disease and its therapy. As more progress is being made and deeper responses are being attained, the disease might turn into a potentially curable one in the near future

Hemorrhagic cardioembolic stroke secondary to a left ventricular thrombus: a therapeutic dilemma

Cardiogenic embolism is a major cause of stroke and often leads to significant morbidity and mortality. Despite the recent advances in our understanding of the pathophysiology of stroke and its risk factors, diagnosis and therapy; some case scenarios still present a real challenge for the treating physicians. We report a case of a 50 year old male patient presenting with multi-territory cerebral infarctions due to a left ventricular mobile thrombus complicated with hemorrhagic transformation at the time of presentation. Gradual introduction of anticoagulation coupled with a multidisciplinary team approach advocating careful daily clinical assessment of the patient and regular echocardiographic and neuroimaging studies have resulted in a better management and achievement of therapeutic goals

Genital ulcer development in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid: a case series

We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid [ATRA] for the treatment of acute promyelocytic leukemia [APL]. Between October 2007 and March 2010, three males and one female [age range 19-35 years] were identified to have genital ulcers after being prescribed all-trans retinoic acid [ATRA] as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted

Side effects of deferasirox iron chelation in patients with beta thalassemia major or intermedia

Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox [DFX] side effects in patients with thalassemia major or intermedia. A retrospective study of 72 patients [mean age: 20.3 +/- 0.9 yrs; 36 male, 36 female] with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise[s] in serum creatinine [7 patients; 40% mean serum creatinine rise from baseline], feeling unwell [2], severe diarrhea [1], pregnancy [1], death unrelated to chelator [2] and rise in serum transaminases [2]. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* [p=0.013]. Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings

Myelomatous pleural effusion. Case report and review of the literature

Plasma cell myeloma is an uncommon disease which, besides primarily involving the bone marrow, has a tendency to involve other organs thus presenting with different clinical manifestations. While pleural effusions are infrequent in this disease, true myelomatous pleural effusions are extremely rare. We report the case of a middle-aged Omani man with relapsed plasma cell myeloma who developed bilateral pleural effusions. The diagnosis of myelomatous pleural effusion was made by finding many abnormal plasma cells as well as a high level of a monoclonal protein [IgG k] in the pleural fluid. In spite of a good initial response to therapy, the patient had progressive disease and died 6 months later with bacterial sepsis. We present a review of the literature that indicates the rarity of such a manifestation and its association with poor prognosis and short survival