Therapeutic Potentials of IL-10 versus IL-12

Cytokines are low molecular weight proteins having roles in essential biological processes, particularly for the immune system. As they have a key role to play, an abnormality in their function can lead to wide variety of diseases (clinical consequences). Thus using the cytokines as therapeutic targets has been an area of active research. Of the entire family, we would like to shed light on two major ones IL-10 and IL-12 having an array of roles in cellular response to infection and autoimmunity. IL-12 is a pro-inflammatory cytokine that has been shown to enhance IFN-γ producing T cell responses and has been widely tested as a vaccine adjuvant. Many studies have shown that IL-12 acts as a link between innate and adaptive immunity by inducing IFN-γ production and polarizing naive CD4 T cells to become Th1 cells. It also has roles in CD8 T cell differentiation. On the other hand, IL-10 is an anti-inflammatory cytokine and has role in maturation of memory CD8 T-cell. It also plays a critical role in preventing autoimmunity and also limits tissue injury by interfering with the intensity and duration of immune response. We would thus like to discuss in details about the therapeutic use of these cytokines for infections as well as diseases such as cancer, autoimmune disorders etc

FACTORS INFLUENCING ADHERENCE TO IMATINIB IN INDIAN CHRONIC MYELOID LEUKEMIA PATIENTS: A CROSS-SECTIONAL STUDY

Adherence to imatinib(IM) is of utmost importance in patients with chronic myeloid leukemia(CML) to maximise treatment effectiveness. The main objective is to measure adherence to    IM & to evaluate individual patient characteristics, personal, treatment related &                    psychological factors influencing adherence behaviour. Hundred patients  receiving IM were analysed for adherence behaviour using 9 item Morisky Medication Adherence Scale              (9-MMAS) . Various factors were assessed for their impact on adherence behaviour.  These   factors were age, gender, duration of treatment, frequency & dosing of treatment, use  of        tobacco & alcohol, educational qualification,employment status,monthly  income, side effects, financial assistance in treatment, social support, knowledge about medicine & disease,         concomitant drug burden, polypharmacy, physician patient interaction, patient  educational    sessions & prevalence of depression. Seventy five percent of patients were found to be           adherent. On univariate analysis, prevalence of depression (p<0.000001), moderate severe     depression (p<0.000001), concomitant drug burden (p=0.036) & monthly income (p=0.015) were found to be significantly influencing adherence. The final multivariate model retained   prevalence of depression with OR= 10.367  (95% CI, 3.112- 34.538) as independent predictor of adherence to therapy. This study suggests that identification & treatment of depression among CML patients may further enhance adherence to IM therapy. Keywords: Chronic Myeloid Leukemia, Adherence, Imatinib, Nine Item Morisky Medication Adherence Scale, Patient Health Questionnaire -9

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study

AbstractWe conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality

Management of B-cell lineage acute lymphoblastic leukemia: expert opinion from an Indian panel via Delphi consensus method

IntroductionCurrently, there are no guidelines for the management of B-cell lineage acute lymphoblastic leukemia (B-ALL) from an Indian perspective. The diagnostic workup, monitoring, and treatment of B-ALL vary among different physicians and institutes.ObjectiveTo develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings.MethodsModified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 experts from India constituted the panel. Clinically relevant questions belonging to three major domains were drafted for presentation and discussion: (i) diagnosis and risk assignment; (ii) frontline treatment; and (iii) choice of therapy (optimal vs. real-world practice) in relapsed/refractory (R/R) settings. The questionnaire was shared with the panel members through an online survey platform. The level of consensus was categorized into high (≥ 80%), moderate (60%–79%), and no consensus (&lt; 60%). The process involved 2 rounds of discussion and 3 rounds of Delphi survey. The questions that received near or no consensus were discussed during virtual meetings (Delphi rounds 1 and 2). The final draft of the consensus was emailed to the panel for final review.ResultsExperts recommended morphologic assessment of peripheral blood or bone marrow, flow cytometric immunophenotyping, and conventional cytogenetic analysis in the initial diagnostic workup. Berlin–Frankfurt–Münster (BFM)–based protocol is the preferred frontline therapy in pediatric and adolescent and young adult patients with B-ALL. BFM/German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia–based regimen is suggested in adult patients with B-ALL. Immunotherapy (blinatumomab or inotuzumab ozogamicin) followed by allogeneic hematopoietic cell transplantation (allo-HCT) is the optimal choice of therapy that would yield the best outcomes if offered in the first salvage in patients with R/R B-ALL. In patients with financial constraints or prior allo-HCT (real-world practice) at first relapse, standard-intensive chemotherapy followed by allo-HCT may be considered. For subsequent relapses, chimeric antigen receptor T-cell therapy or palliative care was suggested as the optimal choice of therapy.ConclusionThis expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings

Haploidentical stem cell transplant: Established treatment, expanding horizons

Haploidentical stem cell transplantation offers an oppurtunity for transplant for almost all patients for whom transplant is indicated. Traditionally, it is associated with higher incidence of graft failure, graft vs host disease and non relapse mortality as compared to matched donor transplant. However, recent advances in the field have tried to mitigate these issues and offer haploidentical transplant as a safe and viable option. In this review, we shall discuss the basics of haploidentical transplantation, how to choose the best donor amongst various haploidentical donors available and understand the various recent advances in the field of haploidentical transplantation and how they addressed the problems associated with it and make it a feasible alternative to matched sibling or unrelated transplant in various diseases

Efficacy and safety of nelarabine in patients with relapsed or refractory T-cell acute lymphoblastic leukemia: a systematic review and meta-analysis

Nelarabine is approved for the treatment of relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) patients who relapse following at least two different chemotherapy regimens. Previous studies have evaluated the efficacy and safety of nelarabine with chemotherapy in the treatment of R/R T-ALL. However, the results are inconsistent. This review aimed to summarize findings on efficacy and safety data in R/R T-ALL patients administered with the drug nelarabine. The present review conducted a comprehensive search of MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until 15 January 2022. Thirteen studies fulfilled the eligibility criteria with a total of 2508 patients. The efficacy of nelarabine was studied in terms of complete remission (CR) and partial remission (PR). Included studies reported overall random-effects pooled prevalence of CR and PR were 37.2 (95% CI: 22.8, 51.5) and 10.2 (95% CI: 4.9, 15.5), respectively. Most common adverse events associated with nelarabine were neutropenia, thrombocytopenia, fatigue, infections, and reversible peripheral neuropathy. Nelarabine is being used as salvage therapy as a bridge to hematopoietic stem cell transplantation and the findings of this meta-analysis indicate that it is an effective and safe treatment to be used in addition to the first-line treatment for R/R T-ALL