Supportive care and symptom management in patients with advanced hematological malignancies: a literature review.

BACKGROUND AND OBJECTIVE: Recent advances have led to cure or long-term disease control for patients with hematological malignancy (HM). Unfortunately, some of them still have poor prognoses and are often associated with significant symptom burden and poor quality of life for patients and families. These patients usually require supportive care including red blood cell and platelet transfusion, due to disease itself and the oncological treatment, apart from their symptom management. However, there is currently lack of the literatures review in these aspects. The objective of this review is to summarize practical supportive care recommendations for physicians or nurses practicing in palliative care (PC)/hematology-oncology unit, starting with core approaches in use of blood products for anemia and thrombocytopenia, management of tumor lysis syndrome, PC and oncology nursing care. METHODS: Evidence for this review was obtained from a search of the Cochrane database, PubMed, guidelines of European Society of Medical Oncology, British society of Hematology, American Society of Clinical Oncology, National Comprehensive Cancer Network and peer-reviewed journal articles. KEY CONTENT AND FINDINGS: For asymptomatic cancer patients who are anaemic, a threshold of haemoglobin level of 7 g/dL is considered to be safe and generally favored for blood transfusion. 'Single-unit' red cell transfusion is safer and at least as effective as 'double-unit' transfusion. Prophylactic platelet transfusion should be given to stable patients without bleeding and with platelet count less than 10×109/L. In febrile patients, the threshold is lifted to 20×109/L. There are also recommendations for the use of blood products during COVID-19 pandemic. In general, HM patients were more prone to painful infections when compared with solid cancer patients. Thus, antibiotics to treat underlying infections should be applied whenever possible and as required to control pain. CONCLUSIONS: This narrative review showed the recent literatures in the supportive care and symptom management of advanced HM patients. However, it is limited by some of the 'evidence-based' recommendations for interventions (including symptom management) based on early phase of HM populations rather than those receiving end-of-life care.

FDG-PET in suspected dementia with Lewy bodies: a case report.

BACKGROUND: Dementia with Lewy bodies (DLB) is still underdiagnosed or mistaken for other types of neurodegenerative diseases. Biomarkers such as 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) can be helpful. CASE PRESENTATION: A 72-year-old gentleman presented with postural hypotension, hallucination, Parkinsonism and recurrent falls. He also had rapidly progressing cognitive impairment. CT and MRI brain showed atrophy of the frontal lobes with preservation of the hippocampi. FDG-PET was suggestive of DLB. He was subsequently treated with Rivastigmine, with significant improvement of his symptoms. CONCLUSION: This case highlights the challenges in diagnosis of an elderly patient with DLB, the use of neuro-imaging as a diagnostic biomarker, the avoidance of the use of antipsychotic and the response to pharmacological treatment with Rivastigmine after a probable diagnosis of DLB.

Mania following antidepressant discontinuation in depression: two case reports.

OBJECTIVE: Antidepressant-induced mania and an antidepressant discontinuation syndrome are well documented, whereas mania occurring after antidepressant cessation has been infrequently reported. METHOD: We describe antidepressant discontinuation-related mania in two Chinese patients, as well as a review of the literature on this phenomenon in unipolar depression. RESULTS: A 72-year-old man and a 65-year-old woman had late-onset depression with vascular risk factors, but no personal or family history of mood disorders. Manic symptoms started after stopping escitalopram and venlafaxine during depressive relapse, and resolved with the initiation of olanzapine and valproate. In the literature, 29 episodes of antidepressant discontinuation-related mania were reported. Tricyclic antidepressants were most frequently implicated, followed by selective serotonin reuptake inhibitors. There was spontaneous resolution of manic symptoms in half of the cases. CONCLUSION: This is the first report of antidepressant discontinuation-related mania in an Asian population, in the setting of late-onset depression. This phenomenon is rare and is amenable to standard treatment.

Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study.

PURPOSE: To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement. PATIENTS AND METHODS: Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients. RESULTS: Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%). CONCLUSION: Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

Mitochondrial D-loop polymorphisms and mitochondrial DNA content in childhood acute lymphoblastic leukemia.

The mitochondrial displacement loop (D-loop) controls mitochondrial expression, with mutations and mitochondrial DNA (mtDNA) content linked to oncogenesis. We investigated D-loop polymorphisms and mtDNA content in childhood acute lymphoblastic leukemia (ALL). The D-loop was sequenced in 251 children: precursor B ALL (n=114), with 76 paired remission/relapse samples; T-ALL (n=24); cord blood controls (n=113). The mtDNA copy number was analyzed using real-time quantitative polymerase chain reaction for 92 controls and 54 ALL patients at diagnosis and remission. Polymorphisms around H-strand replication origin (nucleotides 150 to 199) and conserved sequence block II (nucleotides 299 to 317) were associated with leukemia biology and treatment response. T-ALL patients were more likely to have longer nt303 poly-C tract. T199C polymorphism was associated with increased risk of ALL in Malays; T152C was more frequent in good responders. There was no difference in mtDNA content between diagnostic ALL samples and controls; however, there was significant decrease in mtDNA content after treatment, especially in samples with OH polymorphisms. Somatic mutations were found in 13% (9 of 76) of patients, suggesting a link to leukemogenesis. Our results suggest that polymorphisms impacting transcriptional control could affect mtDNA replication. Decrease in mtDNA content after treatment may confer susceptibility to chemotherapy and be a clue to the good prognosis of childhood ALL.

Minimal residual disease (MRD) measurement as a tool to compare the efficacy of chemotherapeutic drug regimens using Escherichia Coli-asparaginase or Erwinia-asparaginase in childhood acute lymphoblastic leukemia (ALL).

BACKGROUND: L-asparaginase is a crucial drug in childhood acute lymphoblastic leukemia (ALL) induction therapy, but much debate remains regarding the optimal formulation and dosage. As minimal residual disease (MRD) can accurately measure extremely low levels of lymphoblasts, it is a sensitive reflection of leukemia cell kill. We utilized MRD to compare the efficacy of Erwinia-asparaginase (Erwinia-asp) and E. coli-asparaginase (E. coli-asp) during induction therapy for childhood ALL. PROCEDURE: Of 116 precursor-B ALL patients, 22 were treated with Erwinia-asp, 90 with E. coli-asp, and 4 were switched from E. coli-asp to Erwinia-asp. MRD levels at the end of induction were analyzed for 90 patients (Erwinia-asp = 16; E. coli-asp = 74). Patients were stratified into MRD > or =10(-2), between 10(-2)-10(-4) and < or =10(-4). Toxicity information during induction was available for 110 patients. RESULTS: MRD was the only significant prognosticator compared to conventional criteria. Patients treated with Erwinia-asp were 6.7 times more likely to have MRD levels > or =10(-2) (P = 0.031), reflecting slower lymphoblast clearance. While non-asparaginase related toxicities were similar in both groups, more E. coli-asp patients experienced severe asparaginase-related toxicity. CONCLUSION: E. coli-asp is superior to Erwinia-asp in childhood ALL induction. Although E. coli-asp is more toxic, this is balanced by better response to therapy. Early response to treatment as measured by MRD is a direct reflection of leukemic cell kill and is a significant prognosticator of eventual outcome, making it a good surrogate marker to evaluate the efficacy of induction drugs in childhood ALL.