Attenuated adiponectin, omentin, increased interleukin-6 and tumor necrosis factor-alpha levels with altered cognition and depression in non-Hodgkin lymphoma patients: A case-control study.

BACKGROUND AND PURPOSE: Immune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes. METHODS: This case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy. RESULTS: Mean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control. CONCLUSION: Our results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life.

Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes.

Significant heterogeneity has been reported in outcome of Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3::PBX1 in adolescents and adults leading to a lack of consensus on precise risk stratification. We evaluated clinical outcome of 17 adult ALL cases (≥15 years) with this genotype treated on intensive regimes.13/17 received COG0232 and 4/17 cases received UK-ALL protocol. All achieved CR (100%) with above treatment. End of induction MRD was evaluated in 14/17 cases of which 11 (78.5%) achieved MRD negativity. Total nine patients relapsed (7 marrows, 2 CNS). Overall survival at 2 years was 53.3%. The 2 year estimated PFS was 42.9%. The 2 years CIR was 54.2%. Adults with this genotype perform poorly despite early favorable response. Incorporation of novel immunotherapies and prompt HSCT should be strongly considered with this genotype. Targeted NGS panels for additional genetic aberrations can further help in risk stratifying and guiding therapy for this genotype.

HIV Associated Lymphomas: A Double-Edged Sword.

People with HIV (human immunodeficiency virus) are at higher risk of developing Lymphomas in comparison to people without HIV. The risk of developing lymphomas in patients with HIV continues to persist, even in the HAART era. We retrospectively analysed outcomes of patients with HIV associated lymphomas between Jan 2012 and Oct 2022, with minimum follow up of 6 months. Outcomes have been reported in terms of overall response rate (ORR), overall survival (OS) and event free survival (EFS). Statistical methods such as Kaplan Meier test were used to assess the overall survival and progression free survival, while chi-square test was used to assess factors affecting disease response. Twenty-three patients were identified as HIV associated lymphoma in that duration. Four patients were excluded from the cohort due to insufficient data in the database record. 12 (63.15%) were male and 07 (36.85%) were females with male: female ratio of 1.7:1. Median age was 42 years ranging from 21 to 66 years. 11 (57.9%) patients had stage-4 disease at presentation. Median CD4 counts at diagnosis was 615/µl, ranging from 130 to 1100/µl. DLBCL cases were in majority which showed 60% of CR post 1st line Chemotherapy. At the last follow-up, 04 (21.05%) patients were dead and 15 (78.95%) patients were alive. 10 years Overall survival [OS] and Progression Free Survival [PFS] was found to be 78.95% ± 11 at a median follow up of 42.6 months ranging (1.7-114.3) months. HIV associated lymphomas have an acceptable prognosis, despite majority presenting with stage 4 disease, low median CD4 count at diagnosis, concomitant ART, and treatment with intensive chemotherapy.

Short-Term Impact of Hematopoietic Stem Cell Transplantation on Depressive Behavior, Cognition and Quality of Life in Leukemia Patients.

Hematopoietic stem cell transplantation (HSCT) or Bone Marrow Transplantation (BMT) has significantly improved the survival rates of patients suffering from hematological malignancies. However, the cure can only be achieved at the price of morbidity and long-term complications. Thus, this study aimed to evaluate the short-term effect of HSCT on depressive behavior, cognition, and quality of life (QoL) in leukemia patients. Sixty patients were included in this prospective observational study. The current study assessed depression using Patient Health Questionnaire (PHQ-9) scale, cognition using Montreal Cognitive Assessment (MOCA) scale and QoL using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) before 7 days of the therapy i.e., preconditioning/baseline (TP1) and after 30 days of the treatment (TP2) in leukemia patients undergoing HSCT. At TP2, there was a significant improvement in PHQ-9 (p = 0.001), MOCA (p < 0.0001), functional scale (p < 0.0001) and global health & QoL scale (p = 0.001) of EORTC QLQ C30 scores whereas there was a significant decrease in symptom scale of EORTC QLQ C30 score (p = 0.005). Furthermore, at TP2 a statistically significant (p < 0.05) negative correlation was observed between MOCA and symptom scale of EORTC QLQ C30 after Pearson correlation analysis. In conclusion, post-30 days of HSCT there was alleviation in depressive behavior, cognition, and QoL in leukemia patients compared to before therapy.

Spectrum of infections in different regimens of post-induction chemotherapy in acute myeloid leukemia (de-novo): A comparative retrospective study.

Background: Patients diagnosed with acute myeloid leukemia (AML) face a heightened susceptibility to infections, which significantly elevates their risk of mortality and disability. The intensity of the chemotherapy treatment and its specific focus on inhibiting myeloid cell divisions render patients especially vulnerable, particularly during the early stages of chemotherapy. This vulnerability is compounded by the occurrence of repeated episodes of prolonged neutropenia, leaving patients highly susceptible to infections. The compromised immune systems of these individuals make them more susceptible to infections, which adversely affect their physical health and overall well-being. Consequently, our study aimed to investigate the range of infections experienced by patients with newly diagnosed AML undergoing different induction chemotherapy. Methods: This was a comparative retrospective study, conducted at a tertiary hospital providing comprehensive cancer care in North India. All newly diagnosed patients with AML, who received induction chemotherapy from January 1, 2012 to November 1, 2022, were identified from the hospital database and included in this study. Results: Four hundred and twenty AML patients treated with either high-intensity or low-intensity induction chemotherapy was observed in this study. It was found that patients who received high-intensity treatment had a higher rate of clinically and microbiologically documented infections, fever without a known cause, and more cases of febrile neutropenia than those who got low-intensity treatment. These differences between the two groups were particularly evident on day 14 (p = 0.0002) and persisted through day 28 (p = 0.005). Conclusions: These findings underscore the effectiveness and downside of high-intensity induction chemotherapy regimens, as evidenced by the higher incidence of infections observed. Further investigation through prospective clinical studies is warranted to better evaluate and validate the efficacy of this approach.

Effect of antibiotic de-escalation on clinical outcomes in patients with carbapenem-resistant Enterobacteriaceae bacteremia (CRE) in the hematology-oncology setting.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor outcomes, particularly among hematology-oncology patients. Appropriate use (selection and de-escalation) of antibiotics is a key component of management of febrile neutropenia particularly in high CRE prevalence regions like India. Methods: This was a retrospective study done (April 2019-December 2021) in a dedicated oncology center in North India, which assessed the case records of the patients undergoing therapy for hematological malignancies who were diagnosed with CRE bacteremia. Demographic, clinical and microbiological data, as well as antibiotic prescription patterns were studied. Inter-group analysis was done between an antibiotic stewardship cohort (avoiding CRE therapy empirically or stopping CRE therapy if cultures negative; as per suggestions of the AMS team) and a non-antibiotic stewardship cohort (continuation of empirical CRE therapy; de-escalation advice was not followed). Results: A total of 139 patients were identified, with median age of 41 years (range 13-74) out of which 82 (58.9%) were males. Acute myeloid leukemia (66.2%) was the most common malignancy, followed by lymphoma (8.6%) and myeloma (8.6%). Nearly 30% of patients were post allogenic stem cell transplant. Klebsiella pneumoniae was the predominant organism (78.4%) and combination of NDM+OXA-48 (46.3%) was the most common carbapenemase gene detected followed by OXA-48 alone (34.7%). Overall, 28-day mortality was 26.6%. On binary logistic regression analysis, lack of compliance with antibiotic stewardship intervention was an independent predictor of mortality (p=0.005). Conclusions: Prior exposure to empirical CRE therapy or failure to de-escalate was associated with poor outcomes in patients with CRE bacteremia, which gives us a window of antibiotic stewardship in febrile neutropenia.

Recommendations for the treatment and management of adult B-Cell acute lymphoblastic leukemia in Asia-Pacific: Outcomes from a pilot initiative.

The outcomes of adult B-cell acute lymphoblastic leukemia (ALL) remain poor. Recent advancements in the field of leukemia research show potential for improved patient care. However, the adoption of research findings into clinical practice is fraught with practice- and country-specific challenges. The continued addition of new findings warrants critical evaluation for the feasibility of incorporation into clinical practice. A uniform set of evidence-based guidelines can favorably assist physicians in making optimal clinical decisions. Such a resource may also serve as a reference point for strategic planning of initiatives aimed at addressing critical barriers in the optimal management of B-cell ALL. This initiative was undertaken to seek a collaborative perspective and understand the existing challenges. Concordance-based recommendations were outlined through a systematic discussion on various aspects of treatment and management of adult B-cell ALL. The outcomes and experiences gained from this exercise will serve as a foundation for future efforts encompassing the more granular aspects of the management of B-cell ALL across the Asia-Pacific region.

Second stem cell transplantation for treatment of relapsed/refractory multiple myeloma after first autologous stem cell transplant: A 15-year retrospective institutional analysis.

Background: Multiple myeloma remains an incurable disease, with the majority of patients relapsing after autologous stem cell transplant (ASCT). After relapse, second transplant remains one of the therapeutic options, along with novel agents. Methods: We reviewed the data of our patients who underwent ASCT for myeloma (N = 202) over the last two decades (2004-2019). Of these, 12 patients underwent a second transplant. Results: Out of 12 patients, nine underwent second autologous stem cell transplant, whereas three received an allogeneic stem cell transplantation (Allo-SCT). Median progression-free survival (PFS) after the first ASCT was 32 months (5-84 months). Median interval between both the transplants was 35 months (4-159 months). Median age of our cohort which underwent second transplant was 56 years. Overall response rate (ORR) post-second transplant on day +100 was 83.3%, without any transplant-related mortality (TRM). With the use of preemptive plerixafor, none of our patients required a second day for stem cell harvest. Median CD34 dose of stem cells infused was 4.11 × 106/kg. Similar to the first ASCT, the median time to neutrophil and platelet engraftment was 11 and 12 days, respectively. At a median follow-up of 41 months, estimated 3-year PFS and overall survival (OS) was 37% ± 15% and 63% ± 15%, respectively. Conclusion: ">Among all relapsed myeloma patients who were transplant eligible, 11% underwent a second transplant. Second transplant is well tolerated with similar time to engraftment after first ASCT. Hence, we believe that second transplant is a feasible, cost-effective option in a resource-limited setting, which should be more widely utilized.

FLAG based v/s Standard 3 + 7 induction therapy in treatment naïve Acute Myeloid Leukemia: Time to think "beyond anthracyclines".

Daunorubicin and Cytarabine (DA; 3 + 7) has been the standard frontline Acute Myeloid Leukemia (AML) induction regimen resulting in Complete Remission (CR) rates of 50-70%. It is associated with induction mortality of 15-30%. We report a comparative analysis of DA versus fludarabine, cytarabine, G-CSF (FLAG) + /- Venetoclax in resource constrained settings. We conducted a single center, retrospective analysis of 37 treatment naïve fit AML patients from May 2021 to December 2022 who received either standard DA regimen (Group 1) or FLAG + /- Venetoclax (Group 2). The median patient age was 36.6 years in DA arm (n = 18) as compared to 40.1 years in FLAG arm (n = 19). CR rates at day 28 were 55.5% in group 1 and 89.4% in group 2 (odds ratio [OR], 7.20; 95% confidence interval [CI], 1.274 -40.678; P = 0.012). Patients in FLAG based therapy arm had shorter duration of neutropenia (P = 0.003), fewer episodes of grade 3 febrile neutropenia (P = 0.0228), shorter duration of antibiotic therapy (P = 0.03), lesser need of 3rd line antibiotic therapy (P = 0.0228). Mortality rates were 16.6% (n = 3) in (group 1) and 0% (n = 0) in (group 2) (p = 0.105). Our analysis supports that FLAG based induction regimen is an effective and well-tolerated therapy in treatment naïve fit AML patients.

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

Introduction: Currently, 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. Objective: To develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings. Methods: Modified 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 (< 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. Results: Experts 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. Conclusion: This expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings.

Effect of Imatinib treatment on renal anaemia in chronic myeloid leukemia patients.

PURPOSE: In this study, we investigate renal function and anaemia during imatinib treatment in patients with chronic myeloid leukaemia. METHODS: The patients with chronic myeloid leukaemia with chronic phase who had been treated with only imatinib for 12 months at Rajiv Gandhi Cancer Institute and Research Centre (New Delhi, India) were enrolled and prospectively analysed. The chronic renal impairment parameters, including estimated glomerular filtration rate and haemoglobin levels for anaemia from June 2020 to June 2022, were monitored in newly diagnosed in patients with chronic myeloid leukaemia-chronic phase. The data were analysed by SPSS software version 22. RESULTS: In total 55 patients with chronic myeloid leukaemia chronic phase who had been on imatinib for 12 months were monitored. The mean estimated glomerular filtration rate was significantly decreased (74 ± 14 to 59 ± 12 mL/min/1.73m2, p < 0.001) with a decrease in mean haemoglobin levels after 12 months (10.9 ± 2.01 to 9.0 ± 1.02, p < 0.004). The decreased estimated glomerular filtration rate was negatively correlated with haemoglobin levels after 1 year of imatinib administration (correlation coefficient = 0.892, R2 = 0.7976, p < 0.05). CONCLUSION: We recommended close monitoring of renal function and haemoglobin levels in patients with chronic myeloid leukaemia patients.

Risk of Mortality in Bone Marrow Transplant Patients During SARS-CoV-2 Infection: A Systematic Review.

OBJECTIVES: Recipients of bone marrow transplant with COVID-19 are at high risk of mortality and morbidity from their underlying immunocompromised state. Graft-versus-host disease and other comorbidities lead to poor COVID-19 outcomes in these patients. Understanding the outcomes and clinical characteristics of bone marrow transplant recipients with COVID-19 is needed to devise potential life-saving therapies for patients with hematologic malignancies. Reviewing large data sets from different ethnic groups and regions can lead to better understanding. We conducted a systematic review ofreal-world data from prospective and retrospective observational cohort studies that reported the clinical outcomes of COVID- 19 in bone marrow transplant patients. MATERIALS AND METHODS: We used electronic databases (PubMed, ScienceDirect, Google Scholar), with a cut off date of May 31, 2022, to conduct our search. After screening 349 articles, we selected 33 original reports for screening. After screening these articles for eligibility criteria, we selected 12 studies for final data extraction. We extracted data per the preferred reporting items followed for systematic reviews. Quality evaluation was done with a Cochrane risk-of bias tool for nonrandomized studies (ROBINS-1). RESULTS: Bone marrow transplant recipients with COVID-19 experienced poor disease outcomes and high mortality rates. Patient age, immunosuppressant intensity, and presence of graft-versus-host disease or other underlying comorbidities directly affected mortality rates of bone marrow transplant recipients with COVID-19. Other factors, like type of malignancy, type of transplant, and time between transplant and COVID-19 diagnosis, did not affect mortality or poor outcomes of COVID-19. CONCLUSIONS: Bone marrow transplant recipients have a higher risk of mortality and poor disease outcomes from COVID-19. Because curative therapies for COVID- 19 are not available, the only option available is its prevention. Transplant centers worldwide, as pertheir capacities, should develop and adhere to strict standard operating procedures based on international or national guidelines related to transplant recipients with COVID-19.