The co-occurrence of JAK2 V617F mutation with BCR-ABL reciprocal translocation is uncommon. We report a 60-year-old man who initially presented with phenotype of polycythemia vera (PV), which evolved into chronic myeloid leukemia and back to PV once treatment with imatinib was commenced. JAK2 V617F mutation and BCR-ABL fusion transcripts were detected in the initial sample. However, JAK2 V617F alleles diminished when BCR-ABL mRNA burden increased and reappeared once the patient was commenced on imatinib. The dynamic interaction between JAK2 V617F and BCR-ABL implies that two independent clones exist with the JAK2 V617F clone only achieving clonal dominance when BCR-ABL positive clones are suppressed by imatinib.
Within the Asian populations, Indian patients had been reported to require higher warfarin dose compared with the Chinese and Malay patients, and this could not entirely be explained by cytochrome P450 (CYP)2C9 gene variants. Genetic variants of vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1) has been well established as one of key determinants in the different responses of warfarin amongst patients. Adult patients who attended an anticoagulation clinic with stable INR were recruited. VKORC1 and CYP2C9 genotype were sequenced, and clinical characteristics were assessed. A total of 91 Malays, 96 Chinese, and 46 Indian patients were recruited. The mean age was 55 years and 51.5% were males. The mean dose of warfarin for all patients was 3.7 mg, and the mean daily dose of warfarin was significantly higher in Indians compared with the Chinese and Malay patients, 4.9 versus 3.5 and 3.3 mg, respectively (p < 0.001). VKORC1 GG genotype was more commonly seen in Indian patients. The mean warfarin dose in patients with GG genotype required a significant higher warfarin dose compared with those with AG and AA genotype (4.9 vs. 3.7 vs. 3.1 mg, respectively; p < 0.001). CYP2C9*2 and *3 is associated with a lower maintenance dose, 2.9 versus 3.7 mg in CYP2C9*1; p < 0.01. In multivariate analysis, age, ethnic groups, and genotypes had a significant influence on the required warfarin dose. In conclusion, VKORC1 and CYP2C9 polymorphism contribute to the difference dose requirement amongst the patients but other additional possible factors may play a role in the Indian race.
Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on the vertebral bodies, together with intraspinal masses causing spinal cord compression. The patient immediately underwent radiotherapy, and was treated with all-trans retinoic acid and idarubicin. Reassessment MRI showed complete resolution of all intraspinal masses and the disappearance of most of the bony lesions. Post-treatment bone marrow aspirate showed complete hematological and molecular remission. The motor power of his legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level persisted.
The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
Background: The geriatric population in Malaysia is predicted to increase from 4% of the total population in 1998 to 9.8% by 2020, in parallel with developments in the socioeconomy. Cancer is expected to be a major medical issue among this population. However, the decision for treatment in Malaysia is always decided by the caregivers instead of the elderly patients themselves. Objective: The aim of the study was to assess the willingness to accept chemotherapy among elderly Malaysians. Materials and Methods: In this cross-sectional study, patients aged 60 and above from various clinics/wards were recruited. Those giving consent were interviewed using a questionnaire. Results: A total of 75 patients were recruited, 35 patients (47%) with a history of cancer. The median age was 73 years old. There were 29 Chinese (38.7%), 22 Indian (29.3%), 20 Malay (26.7%) and four other ethnicity patients. Some 83% and 73% of patients willing to accept strong and mild chemotherapy, respectively. Patients with cancer were more willing to accept strong and mild chemotherapy compared to the non-cancer group (88.6% vs 62.5%, P=0.005, 94% vs 80%, P=0.068). On sub-analysis, 71.4% and 42.9% of Chinese patients without a history of cancer were not willing to receive strong and mild chemotherapy, respectively. Conclusions: The majority of elderly patients in UMMC were willing to receive chemotherapy if they had cancer. Experience with previous treatment had positive influence on the willingness to undergo chemotherapy.
Background:The use of warfarin in patients with non-valvular atrial fibrillation (NVAF) can be challenging. In this study, we evaluate the time in therapeutic range (TTR), health-related quality of life (HRQoL) and treatment satisfaction of patients on long-term warfarin for NVAF. The HRQoL and treatment satisfaction were compared based on the TTR.Methods:A cross-sectional study was conducted among patients on warfarin for NVAF who attended the anticoagulant clinic of a tertiary cardiology referral center in Sarawak from 1st June 2018 to 31st May 2019. Patients’ TTR was calculated by using Rosendaal technique, while their HRQoL and treatment satisfaction were assessed by using Short Form 12 Health Survey version 2 (SF12v2) and Duke Anticoagulant Satisfaction Scale (DASS), respectively. Results: A total of 300 patients were included, with mean TTR score of 47.0 ± 17.3%. The physical component summary (PCS) and mental component summary (MCS) score of SF-12v2 were 47.0 ± 9.0 and 53.5 ± 9.6, respectively. The total score for DASS was 55.2 ± 21.3, while the score for limitations (L), hassles and burdens (H&B) and positive psychological impacts (PPI) were 18.0 ± 10.0, 15.6 ± 9.1 and 21.6 ± 5.9, respectively. Seventy-three (24.3%) patients had good TTR (≥ 60%), with mean of 70.2 ± 8.7%; while 227 (75.5%) patients with poor TTR had significantly lower mean of 39.5 ± 11.9% (p = 0.006). There was no significant difference in the score of PCS (p = 0.150), MCS (p = 0.919) and each domain of SF-12v2 (p = 0.184 – 0.684) between good and poor TTR, except for social functioning (p = 0.019). The total DASS score was also not significantly different between group (p = 0.779). Similar non-significant difference was also reported in all the DASS sub dimensions (p = 0.502 – 0.699).Conclusions:Majority of the patients on long-term warfarin for NVAF in the current study have poor TTR. Their HRQoL and treatment satisfaction are independent of their TTR. Achieving a good TTR do not compromise the HRQoL and treatment satisfaction. Therefore, appropriate measures should be taken to optimise INR control, failing which direct oral anticoagulant therapy should be considered.
In recent years, considerable progress has been made in the standard treatment for chronic lymphocytic leukaemia (CLL) due to the availability of new potent drugs. However, the majority of data on CLL were derived from Western populations, with limited studies and guidelines on the management of CLL from an Asian population perspective. This consensus guideline aims to understand treatment challenges and suggest appropriate management approaches for CLL in the Asian population and other countries with a similar socio-economic profile. The following recommendations are based on a consensus by experts and an extensive literature review and contribute towards uniform patient care in Asia.
Aim To retrospectively report the clinical outcomes of non‐Hodgkin's Lymphoma (NHL) patients post high dose therapy (HDT) with autologous haematopoietic stem cell transplant (AHSCT) and determine whether upfront transplant, which is a first‐line consolidative treatment with induction chemotherapy, would be a feasible modality in a resource‐limited country. Methods The medical records for NHL patients who had undergone HDT followed by AHSCT from October 1997 to November 2016 from two hospitals in Klang Valley, Malaysia were obtained from the medical record database and analysed retrospectively through statistical analysis. Results A total of 148 patients were retrospectively identified post‐AHSCT, where the majority of whom had B cell lymphoma (53.4%). Majority of patients (88.5%) were in complete remission before AHSCT. The overall survival (OS) and event‐free survival (EFS) at 3 years were 68.9% and 60.8%, respectively. The major cause of death was disease progression at 73.9%, while transplant‐related mortality was 15.2%, with a median follow‐up period of 179.5 weeks. Conclusion Our study illustrates the promising outcomes of HDT with AHSCT in NHL patients in a resource‐limited country. We recommend larger studies to be conducted in the future with a longer duration of follow‐up to validate our findings.
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