Polyphenol-Rich Ginger (Zingiber officinale) for Iron Deficiency Anaemia and Other Clinical Entities Associated with Altered Iron Metabolism.

Ginger (Zingiber officinale) is rich in natural polyphenols and may potentially complement oral iron therapy in treating and preventing iron deficiency anaemia (IDA). This narrative review explores the benefits of ginger for IDA and other clinical entities associated with altered iron metabolism. Through in vivo, in vitro, and limited human studies, ginger supplementation was shown to enhance iron absorption and thus increase oral iron therapy's efficacy. It also reduces oxidative stress and inflammation and thus protects against excess free iron. Ginger's bioactive polyphenols are prebiotics to the gut microbiota, promoting gut health and reducing the unwanted side effects of iron tablets. Moreover, ginger polyphenols can enhance the effectiveness of erythropoiesis. In the case of iron overload due to comorbidities from chronic inflammatory disorders, ginger can potentially reverse the adverse impacts and restore iron balance. Ginger can also be used to synthesise nanoparticles sustainably to develop newer and more effective oral iron products and functional ingredients for IDA treatment and prevention. Further research is still needed to explore the applications of ginger polyphenols in iron balance and anaemic conditions. Specifically, long-term, well-designed, controlled trials are required to validate the effectiveness of ginger as an adjuvant treatment for IDA.

Regression of Intermediate-High Risk Monoclonal Gammopathy of Undetermined Significance (MGUS) With Long-term Use of Curcumin: A Case Report.

Patients with intermediate-high risk MGUS are not offered therapeutic options to date and standard of care remains observation with re-evaluations of the patient every 3 to 6 months. Given the persistent risk of progression as well as potential complications experienced by some, and anxiety experienced by most patients, early intervention with non-toxic curcumin, aimed at potentially slowing down or stopping disease progression might be therapeutic. We present here an intermediate-high risk MGUS patient who has been taking curcumin for 16 years and has shown a decrease in disease markers and an increase in uninvolved immunoglobulins, adding to the body of evidence of benefit of curcumin to MGUS patients.

Impact of Phlebotomy on Quality of Life in Low-Risk Polycythemia Vera.

Polycythemia vera is an indolent myeloproliferative disorder that predisposes patients to venous and arterial thrombosis and can transform into myelofibrosis and acute myeloid leukemia. Consistent phlebotomy prevents life-threatening cerebrovascular and coronary artery disease and prolongs survival in low-risk polycythemia vera (patients under 60 years without thrombosis). However, despite its effectiveness in preventing serious complications, phlebotomy does not necessarily enhance the quality of life (QoL). This review assesses QoL issues associated with low-risk PV, explores alternative management strategies such as erythrocytapheresis, and discusses the roles of hydroxyurea, peginterferon, ruxolitinib, and other novel agents in potentially improving disease management and patient outcomes.

Harnessing the Immune System: An Effective Way to Manage Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous hematological disorder with malignant potential controlled by immunological characteristics of the tumor microenvironment. Rapid breakthrough in the molecular pathways has made immunological approaches the main anchor in the management of DLBCL, with or without chemotherapeutic agents. Rituximab was the first monoclonal antibody approved for the treatment of DLBCL. Following rituximab that transformed the therapeutic landscape, other novel immunological agents including chimeric antigen T-cell therapy have reshaped the management of relapsed/refractory DLBCL. However, resistance and refractory state remain a challenge in the management of DLBCL. For this literature review, we screened articles from Medline, Embase, Cochrane databases and the European/North American guidelines from March 2010 through October 2022 for DLBCL. Here we discuss immunological agents that will significantly affect future treatment of this aggressive type of lymphoma.

Insights into the Impact of Hesitancy on Cancer Care and COVID-19.

World Health Organization findings indicate that the COVID-19 pandemic adversely affected cancer diagnosis and management. The COVID-19 pandemic disrupted the optimal management of outpatient appointments, scheduled treatments, and hospitalizations for cancer patients because of hesitancy among patients and health-care providers. Travel restrictions and other factors likely affected medical, surgical, and radiation treatments during the COVID-19 pandemic. Cancer patients were more likely to be affected by severe illness and complications if they contracted COVID-19. A compromised immune system and comorbidities in cancer patients may have contributed to this increased risk. Hesitancy or reluctance to receive appropriate therapy or vaccination advice might have played a major role for cancer patients, resulting in health-care deficits. The purpose of this review is to evaluate the impact of COVID-19 on screening, entry into clinical trials, and hesitancy among patients and health-care professionals, limiting adjuvant and metastatic cancer treatment.

Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and curcumin: a randomized, double-blind placebo-controlled cross-over 4g study and an open-label 8g extension study.

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) represent useful models for studying multiple myeloma precursor disease, and for developing early intervention strategies. Administering a 4g dose of curcumin, we performed a randomised, double-blind placebo-controlled cross-over study, followed by an open-label extension study using an 8g dose to assess the effect of curcumin on FLC response and bone turnover in patients with MGUS and SMM. 36 patients (19 MGUS and 17 SMM) were randomised into two groups: one received 4g curcumin and the other 4g placebo, crossing over at 3 months. At completion of the 4g arm, all patients were given the option of entering an open-label, 8g dose extension study. Blood and urine samples were collected at specified intervals for specific marker analyses. Group values are expressed as mean ± 1 SD. Data from different time intervals within groups were compared using Student's paired t-test. 25 patients completed the 4g cross-over study and 18 the 8g extension study. Curcumin therapy decreased the free light-chain ratio (rFLC), reduced the difference between clonal and nonclonal light-chain (dFLC) and involved free light-chain (iFLC). uDPYD, a marker of bone resorption, decreased in the curcumin arm and increased on the placebo arm. Serum creatinine levels tended to diminish on curcumin therapy. These findings suggest that curcumin might have the potential to slow the disease process in patients with MGUS and SMM.

Thrombosis in Myeloproliferative Neoplasms: A Single Center Experience of Using Whole Blood Platelet Aggregation Studies for Risk Assessment and Thromboprophylaxis.

CONCLUSION: Routine use of WBPA studies enables safe and effective risk-adapted thromboprophylaxis in MPN patients, irrespective of the underlying driver mutation and their risk predicted by the IPSET- thrombosis criteria.

Primary immune thrombocytopenia: a 'diagnosis of exclusion'?

Current diagnosis of primary immune thrombocytopenia (ITP) is presumptive, centered on excluding other causes of thrombocytopenia. The diagnosis of ITP is challenging because of the wide range of potential inherited and acquired causes of thrombocytopenia. The treatment of ITP is empiric with steroids, high-dose immunoglobulin, immunosuppressants and thrombopoietin agonists with potential side effects. We searched Medline and Cochrane databases, reviewed the study data and analyzed the individual diagnostic tests for their evidence-based role in the diagnosis of ITP. We then analyzed the strength of the scientific evidence for each diagnostic test in the diagnosis of ITP and identified gaps in the diagnostic accuracy. The diagnostic challenges in ITP include: insufficient evidence for the individual test for diagnosis of ITP, no standardized protocol/guideline for diagnosis, hurdles in accessing the available resources and failure to correlate the clinical data while reviewing the blood smear. We did not identify a diagnostic test that clinicians can use to confirm the diagnosis of ITP. In the absence of a diagnostic test of proven value in ITP, the clinician is best served by a comprehensive history and physical examination, complete blood count and review of the peripheral blood smear in evaluating thrombocytopenia.

Is 6-Shogaol an Effective Phytochemical for Patients With Lower-risk Myelodysplastic Syndrome? A Narrative Review.

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signaling pathways, and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodeling, and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukemia, and iron overload is compounded by blood transfusions given to improve anemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumor activity against leukemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies. The standard dose is 420 mg daily; however, its irreversible binding mechanism allows adequate target blockade at much lower doses due to prolonged effect. Dose reductions or interruptions are often used in clinical practice to limit its distinct side effects, including diarrhea, bleeding and atrial fibrillation and emerging evidence exists that these do not hinder efficacy. Using a retrospective clinical audit of a single-center outpatient hematology clinic, we aimed to examine outcomes and toxicities of a reduced frequency dose regimen of ibrutinib in patients beyond the confines of a clinical trial. METHODS: A small pilot study was conducted on 16 voluntary CLL patients that had achieved partial or complete remission on standard dose ibrutinib and were considering cessation due to side effects. Patients were consented and prescribed a 420 mg thrice weekly regimen and side effects and outcomes were recorded on routine review. A retrospective clinical audit from 2015 to 2018 was then conducted to compare pilot participants to patients that had remained on standard dosing and results from the extended follow-up of the landmark RESONATE trial. RESULTS: None of the 16 patients in the pilot relapsed or died during the study period equating to a 100% progression free and overall survival. There was resolution or reduction in all side effects reported following switchover; however, the study was too small to establish a statistical relationship. CONCLUSION: This is the first study to demonstrate use of a thrice weekly regimen to reduce ibrutinib-related toxicities whilst preserving safety and efficacy in patients following complete or partial remission on standard dose therapy. Higher powered, prospective studies are required to establish positive health and financial implications in the elderly and vulnerable CLL demographic.

Use of Curcumin in Multiple Myeloma patients intolerant of steroid therapy.

Curcumin, when used in a combination regimen in multiple myeloma patients, has comparable progression-free survival without the adverse effects of steroid-based combination therapies that is curcumin may be a viable alternative to corticosteroids in combination with an immunomodulatory drug or proteasome inhibitor.

Flexible low-intensity combination chemotherapy for elderly patients with acute myeloid leukaemia: a multicentre, phase II study.

OBJECTIVE: To evaluate the efficacy of a flexible low-intensity combination chemotherapy (FLICC) protocol in a multicentre, phase II study of elderly patients with acute myeloid leukaemia (AML). METHOD: Twenty-five patients aged 61-78 years (median 70 years) with de novo (n = 17) or secondary (n = 8) AML (cytogenetic risk: favourable 2, intermediate 18, adverse 2, unknown 3) from eight Australian centres were enrolled. Treatment comprised mitoxantrone 6 mg/m(2) intravenously daily for 3 days, cytarabine 10mg/m(2) subcutaneously every 12 hours for 7-14 days and etoposide 100mg orally for 7-14 days. RESULTS: The treatment was generally well tolerated, and 13 patients (52%) achieved a complete remission (CR). One patient achieved a partial remission but died on day 28 due to pneumonia. Five patients (20%) had no response, whilst six (24%) died on or before day 30 and so were not evaluable. The median overall survival (OS) was 6.5 months, and the median remission duration was 7.7 months. Estimated 1-year survival was 32%, but patients achieving CR had an estimated 1-year survival of 64%, whereas none in the non-CR group survived to 1 year. Two of the CR patients have survived beyond 2 years. OS was significantly shorter in the adverse cytogenetic risk group of patients compared with the favourable- and intermediate-risk groups, with the rates of death relative to the adverse group being 0.02 and 0.08 in the favourable- and intermediate-risk groups, respectively. There was no significant association between CR rate and pre-existing myelodysplasia or the presence of multilineage dysplasia. The median durations of significant neutropenia (<0.5 x 10(9)/L) and thrombocytopenia (<20 x10(9)/L) with the first course of treatment in the 19 evaluable patients were 19 days (range 12-26) and 11 days (range 1-25), respectively. The median duration of stay in the hospital was 27 days (range 14-42). These values were much shorter for the second course of treatment: 6 days, 5 days and 15 days, respectively. CONCLUSION: The findings of this multicentre, phase II study validate the previously reported single-institution experience with the FLICC protocol in elderly patients with AML. The clinical outcome with this protocol is comparable to those reported with more aggressive anti-leukaemia protocols.

B-Cell Disorders and Curcumin.

Clinical studies with patients with early hematological malignancies (ie, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or stage 0/1 chronic lymphocytic leukemia) suggest that early intervention with curcumin, derived from the spice turmeric, may lead to prolonged survival and delay in progressive disease in some of these patients.

Effect of the Ginger Derivative, 6-Shogaol, on Ferritin Levels in Patients With Low to Intermediate-1-Risk Myelodysplastic Syndrome-A Small, Investigative Study.

BACKGROUND: Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal stem cell disorders characterized by dysplastic and ineffective hematopoiesis and peripheral cytopenias. Elevated serum ferritin (SF) is often observed in nontransfused, lower risk MDS. It has been reported that ineffective erythropoiesis enhances iron absorption in MDS through downregulation of hepcidin and its prohormones such that SF rises. AIM: To determine the effect of 6-shogaol, a dehydration derivative of ginger, known to have hepatoprotective and chemotherapeutic activity, on 6 early-stage, transfusion-independent patients with MDS, 3 of whom had raised levels of SF. METHOD: Six patients with MDS with low or intermediate-1 subtypes, as defined by the International Prognostic Scoring System (IPSS), were recruited into the study and were administered 1 gel capsule daily containing 20 mg ginger extract standardized for 20% 6-shogaol. Blood and urine samples were collected and various markers monitored at regular intervals. RESULTS: 6-shogaol caused a decrease in SF levels in 3 of 6 patients with early MDS (50%) whose SF levels were elevated at the start of the study. Our findings suggest upregulation of hepcidin and its prohormones, possibly through an improvement in liver function. DISCUSSION: In light of the encouraging results in this small, investigative study, we are planning a larger study to confirm the beneficial effect of 6-shogaol in patients with raised ferritin levels due to ineffective erythropoiesis.

Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia): A Preliminary Clinical Study.

Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies.