Progress in our understanding of multiple myeloma and its treatment has resulted in a more tailored approach to patient management, with different therapeutics regimens for different patient populations. The decision to initiate therapy depends primarily on the presence of symptoms which has to balance the chance of tumor clearance and against the risks of treatment related mortality. Selection of appropriate initial treatment should be based primarily on patient's characteristics (biologic age, co-morbidities), the disease characteristics (tumor burden and genetic risk profile) and the expected toxicity profile of the different regimens. When treatment begins, in younger transplant eligible patients the goal is to achieve high quality responses with intensive therapies as the quality of response appears to be important surrogates for long-term outcome. In the majority of myeloma patients in whom intensive treatment is not an option due to advanced age and co-morbidities, treatment should emphasize on optimal disease control to obtain symptomatic relief and to maintain a satisfactory quality of life. The introduction of novel agents has substantially changed the treatment paradigm of this otherwise incurable disease. The utilization of these drugs has moved from relapse setting to the front line setting and has benefited all patient groups. Because of these rapid developments and many treatment options we need good quality clinical studies to guide clinical practice in the management of patients with multiple myeloma. This review presents an update on current concepts of diagnosis and treatment of patients with multiple myeloma and provides recommendations on tailored therapies with particular reference to the local practice. The information presented herein may be used by the health care providers caring for myeloma patients as a guideline to counsel patients to understand their disease and the treatment better.
The incidence of Non-Hodgkin's lymphomas (NHL) is rising worldwide and if not adequately treated carries a high mortality rate. The pattern and frequency of NHL vary in different populations and geographical regions. It has considerable biologic and clinical heterogeneity and a definitive diagnosis can be made only after histopathogical examination. The histology and the extent of the lymphoma are the major determinants of optimal therapeutic regimen and treatment outcome. Additionally, the overall treatment strategies should be tailored according to medical status and preference of the patient. A holistic approach provided by a multi-disciplinary team of health care professionals is the cornerstone of ensuring successful treatment outcome. Importantly, therapy should be expedited and where possible performed in experienced centers. Patients achieving remission would require long-term monitoring for disease recurrence and late effects of cytotoxic chemotherapy and radiotherapy. Hence, clinicians should have a fundamental understanding in the biology and the principles of treatment of NHL. This review provides an evidence-based and systematic approach in designing therapeutic strategies for individual patients with newly diagnosed and relapsed NHL focusing on the common types of NHL with particular reference to the current practice within the local settings. The role of standard and novel therapeutic modalities in treatment will be summarized.
A patient was admitted for breathlessness associated with post-splenectomy multiple pseudocysts and succumbed after internal drainage of the pseudocyst. Although the occurrence of pseudocyst following splenectomy is uncommon, failure to identify and treat this condition at an early stage could result in fatal consequences. Imaging plays an important role in the diagnosis and management of pseudocyst occurring after splenectomy. The advent of interventional radiology has provided better treatment option for patients with solitary pancreatic pseudocysts with success rates similar to those with open surgery but with lower morbidity and mortality rates. However, its role in the management of multiple pseudocysts remains to be defined.
Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potential curative option for many patients with hematological malignancies (HM). However, the high rate of transplantation-related mortality (TRM) restricted the use of standard myeloablative HSCT to a minority of young and fit patients. Over the past few years, it has become evident that the alloreactivity of the immunocompetent donor cells mediated anti-malignancy effects independent of the action of high dose chemoradiotherapy. The use of reduced intensity conditioning (RIC) regimens has allowed a graft-versus-malignancy (GvM) effect to be exploited in patients who were previously ineligible for HSCT on the grounds of age and comorbidity. Retrospective analysis showed that RIC has been associated with lower TRM but a higher relapse rate leading to similar intermediate term overall and progression-free survivals when compared to standard myeloablative HSCT. However, the long term antitumor effect of this approach is less well established. Prospective studies are ongoing to define which patients might most benefit from reduced toxicity stem cell transplant (RT-SCT) and which transplant protocols are suitable for the different types of HM. The advent of RT-SCT permits the delivery of a potentially curative GvM effect to the majority of patients with HM whose outcome with conventional chemotherapy would be dismal. Remaining challenges include development of effective strategies to reduce relapse rates by augmenting GvM effects without increasing toxicity.
Paroxysmal nocturnal haemoglobinuria (PNH) also known as 'Marchiafava Micheli syndrome' is a rare condition which can lead to both acute and chronic forms of renal failure through renal tubular haemosiderin deposition. A 45-year-old lady with underlying PNH, presented with complaints of fever, productive cough followed by dark coloured urine. Investigations revealed pancytopenia with a markedly raised creatinine from her baseline (from 65 mmol/L to 385 mmol/L) consistent with acute kidney injury (AKI). Renal biopsy confirmed the diagnosis of haeme nephropathy. The renal impairment improved rapidly and normalised over a period of 5 days with alkaline diuresis (AD). The patient did not require haemodialysis unlike most other reported cases of AKI secondary to haeme nephropathy in PNH. This is the second reported case of AKI in PNH which was successfully treated with AD alone emphasizing the role of AD as a promising therapeutic strategy in this condition.
Haematopoietic stem cell transplantation (HSCT) has progressed rapidly since its introduction about five decades ago. There is now an increasing demand for transplant physicians in both public and private domains to perform this procedure in view of significant improvement of remission rates in haematological malignancies and increasing indications of HSCT. Peripheral blood has largely replaced bone marrow as the preferred source of haematopoietic stem cells (HSC). Transplantation-related mortality and morbidity rates have considerably decreased because of improved conditioning regimens, human leukocyte antigen (HLA) typing methods, supportive care, and most importantly, prophylaxis, diagnosis and treatment of serious infections. New transplantation strategies, such as reduced intensity transplantation, have extended the use of allogeneic transplant to patients with older age and co-morbidities. Current efforts are focused on ways to increase the donor pool and to improve the long term outcome of HSCT survivors in particular to reduce the relapse rate and the late effects of HSCT. This article summarizes the sources and procurement of HSC, the types and process of HSCT, indications for HSCT and complications associated with HSCT with particular reference to the current practice within the local settings.
Irreversible optic nerve dysfunction associated with central retinal vein occlusion (CRVO) is an unusual but important complication of Waldenstrom Macroglobulinemia (WM). Acute visual loss in CRVO is mainly due the severe macular oedema. However, ischaemic optic neuropathy needs to be considered in patients with CRVO when, (i) there is a relative afferent papillary defect and central scotoma, (ii) the visual acuity is not consistent with the retinal pathology, and (iii) the visual defects persisted despite resolution of macular oedema following treatment of the hyperviscosity state. The ischaemic type of CRVO is associated with a poor visual prognosis and the presenting visual acuity has a prognostic role. We report the first description of irreversible unilateral optic nerve damage associated with CRVO in a patient with WM.
Owing to the importance of dendritic cells (DC) in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review surveys the heterogeneity of DC with regards to their phenotype and developmental origin, and how they initiate, modify and regulate the immune response, with emphasis on their maturation, migration, antigen-presentation and interaction with T cells and other immune cells. Much of this knowledge is obtained through research on murine DC. Research on human DC has been hampered by limitations associated with in vitro assays and limited access to human tissues. New approaches on human DC research are required in order to develop novel strategies for the treatment of microbial infections, the control of graft rejection, and the improvement of DC-based immunotherapeutic protocols for autoimmunity, allergy, and cancer.
Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the deposition of amorphous non-congophilic materials predominantly in the kidneys leading to nephrotic syndrome or renal failure. As with light chain amyloidosis. MIDD is associated with a paraproteinemia. We report a patient suffering from multiple myeloma with IgG kappa paraproteinemia and immunoglobulin deposits predominantly in the bone marrow. The deposits are both as amorphous non-congophilic materials, and in the form of crystals, an observation not reported before.
A 37-year-old Malay man presented initially with the clinical picture of essential thrombocythaemia (ET) without the extreme leukocytosis, marked splenomegaly and low neutrophil alkaline phosphatase characteristic of chronic myelogenous leukaemia (CML). Bone marrow examination showed massive megakaryocytic hyperplasia; cytogenetic studies showed the presence of Philadelphia chromosome. The patient was treated with hydroxyurea that resulted in reduction in the platelet count. Seventeen months later, he presented with fever associated with tender massive splenomegaly. Bone marrow finding was consistent with chronic phase CML. The presence of a rearrangement involving the major breakpoint cluster region (M-bcr) on chromosome 22 was confirmed by reverse transcriptase-polymerase chain reaction. The clinical importance of finding the Philadelphia chromosome in patients who seem to have ET is in assessing prognosis. ET generally follows a chronic, indolent course. However, this patient who had Philadelphia chromosome underwent clinical transition to chronic phase CML17 months and blast crisis 29 months after presentation.
Breast recurrence of acute lymphoblastic leukaemia (ALL) after stem cell transplant is uncommon, with less than 20 reported cases in the literature. In the majority of cases, the lesions developed without simultaneous involvement of other sites or graft-versus-host disease (GvHD). We describe the first case of simultaneous bilateral breast and ovarian relapses after allografting in ALL, occurring in an 18-year-old female Chinese patient while she was having oral and hepatic chronic GvHD, persistent haematological remission and donor haematopoiesis. She received radiotherapy and chemotherapy, which resulted in resolution of the breast and ovarian lesions, and remained disease free ten months after the onset of the relapse. This case suggests that there may be different mechanisms for bone marrow vs. extramedullary relapses and a complex relationship between GvHD and graft-versus-leukaemia.
Primary oesophageal lymphoma is a very rare entity, with fewer than 30 reported cases worldwide. It represents an important cause of dysphagia. Most of the oesophageal lymphomas are diffuse large B-cell type, with only one reported case of anaplastic large cell lymphoma (ALCL) of T-cell phenotype. Primary oesophageal lymphomas that are not associated with an immunocompromised state tend to affect elderly patients. We describe the first case of primary oesophageal Ki (CD30)-positive ALK+ALCL of T-cell phenotype in a 34-year-old immunocompetent woman, who presented with a two-year history of dysphagia. She was treated with chemotherapy and endoscopic oesophageal dilations and stenting, resulting in complete remission of the lymphoma and resolution of the dysphagia. She then underwent autologous peripheral blood haematopoietic stem cell transplantation and remained disease-free two years after the diagnosis.
Kimura’s disease (KD) is a rare, benign chronic inflammatory disease of unknown aetiology, typically presents in the Orientals as subcutaneous masses in the head and neck region that could be easily misdiagnosed as a malignant tumour, leading to unnecessary radical surgery or intensive cytotoxic therapy. It has been mainly reported in the Chinese and Japanese literature. It is difficult to diagnose before tissue biopsy and fine needle aspiration cytology (FNAC) has limited value. Hence, unless the pathologists are aware of this entity, it might be mistaken as a malignant lesion. We encountered a case of KD in a Malay patient presenting as a parotid mass that was initially diagnosed as Hodgkin’s lymphoma (HL). This disorder should be suspected in young male Asian patients presenting with a painless unilateral mass in the head and neck region with associated hypereosinophilia.
This research was based on the reality that there is no motor ability exercise model for football players with cerebral palsy. The coach has difficulty in handling the physical/motor ability issues, such as falling more easily, difficulty reversing and changing the direction quickly, less balance, and poor coordination. The main research problem is how to develop Motor Ability Exercise Model with Circuit Method for Indonesian CP football team. The research purpose was to produce a special circuit training model for CP football. The study design was used quasi experiment. The research subjects included 12 players of the Indonesian CP Football team for APG Malaysia 2017. The data collection technique used a modification of motor ability test and development (Research and Development). The research was started from November 2016 and has been completed in June 2017. The research result was the development of a motor ability exercise model with the Circuit Method for the Indonesian CP football team, which effectively improved the motor ability of the Indonesian CP Football Team in National Training for the 2017 ASEAN Paragames Malaysia. This included (1) a motor ability exercise model with circuit model for flexibility, (2) a motor ability exercise model with circuit model for strength (3) a motor ability exercise model with circuit model for balance and (4) motor ability exercise model with circuit model for coordination.
Hematopoietic stem cell transplantation (HCT) utilizing non-myeloablative (NMA) and reduced-intensity conditioning (RIC) regimens (collectively referred to as reduced-toxicity HCT, RT-HCT) has become a viable therapeutic option for patients with hematological malignancies who are ineligible for standard myeloablative conditioning transplantation (MA-HCT). RT-HCT has been shown to induce stable engraftment with low toxicity, and to produce similar overall and progression-free survival (PFS) when compared to MA-HCT in acute myeloid leukemia and myelodysplastic syndrome. The best results for RT-HCT have been reported for patients with disease that is in remission, indolent and chemosensitive, and with a strong graft-versus-malignancy effect. Chronic graft-versus-host disease seems to correlate with a lower relapse rate and better PFS. RT-HCT is inferior when performed in poor risk or advanced disease, due to high relapse rates. A search for novel strategies that includes the most appropriate conditioning regimens and post-transplant immunomodulation protocols with more intensive anti-malignancy activity but limited toxicity is in progress. This review provides an update on the results of clinical studies of RT-HCT, and discusses possible indications and investigative strategies for improving the clinical outcomes of RT-HCT for the major hematological malignancies.
Multiple lung cavitations and endobronchial nodules are rare presentations of newly diagnosed and recurrent Hodgkin's disease. The clinical and radiological features can be confused with pulmonary tuberculosis, which can be difficult to exclude in endemic areas. However, the presence of endobronchial nodules point, towards Hodgkin's disease. Differential diagnosis is aided by the fact that these lesions usually respond promptly to specific therapy. We present a case of an adolescent male who had constitutional and pulmonary symptoms associated with pulmonary cavities and endobronchial nodules subsequently confirmed to be Hodgkin's disease.