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.

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.

Busulfan and cyclophosphamide-based conditioning regimen still holds the promise of being a safe and efficacious regimen for allogeneic transplantation in patients with transfusion-dependent thalassemia, even in high risk.

Busulfan and cyclophosphamide (BuCy)-based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan-based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion-dependent thalassemia (TDT) conducted at our institute (2013-2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1-12) and 9 (1-15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2-9.1) versus 5 (1.65-8.01) 106 /kg in Flu/Bu/Cy/ATG versus Treo/Thio/Flu group, respectively. Neutrophils and platelets engrafted at a median of 16 (14-21) and 16 (9-47) days in Flu/Bu/Cy/ATG and 15 (10-20) and 13 (9-41) days in Treo/Thio/Flu group. Median duration of follow-up was 28 (23-32.9) months. Five (6.6%) patients had rejection (all secondary). Venoocclusive disease was observed in 2 (5.7%) versus 4 (10.3%) patients (p = .047), respectively. Flu/Bu/Cy/ATG had 4 (11.4%) patients with acute GVHD versus 15 (38.5%) patients which had significant impact on survival (p = .038). We observed chronic GVHD in 4 (11.4%) and 11 (28.2%) patients, respectively, with significant impact on survival (p = .031). Four (5.1%) patients had TRM in Treo/Thio/Flu group, in contrast to none in Flu/Bu/Cy/ATG group. Mixed chimerism was common in Flu/Bu/Cy/ATG {20 (57.1%)} versus Treo/Thio/Flu group {12 (30.1%)}. Five-year Event Free Survival (EFS) and OS of entire cohort were 87% + 4% and 94% + 3%, respectively. Estimated TFS, EFS, OS of Flu/Bu/Cy/ATG versus Treo/Thio/Flu was 97.1% + 2.9% versus 89.2% + 5.1% (p = .251), 97 + 3% versus 80.7 + 6% (p = .041) and 100% versus 90.4 + 5% (p = .067), respectively. In our experience, Flu/Bu/Cy/ATG regimen is safe and effective even in high-risk TDT. However, one needs to be vigilant for mixed chimerism.

Impact of imatinib treatment on renal function in chronic myeloid leukaemia patients.

BACKGROUND: Recently, multiple epidemiological studies have linked imatinib with the alteration of renal function in chronic myeloid leukaemia (CML) patients. This meta-analysis aimed to summarize the impact of imatinib use on renal function in CML patients. METHODS: A systematic search was conducted on MEDLINE and Embase to identify articles assessing the impact of imatinib exposure on renal function in CML patients. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS). Two authors independently performed literature-screening, risk of bias and data extraction. The risk of renal dysfunction (chronic kidney disease or acute kidney injury) among imatinib users was computed as the primary outcome of interest. The certainty of findings was assessed using the grading of recommendations assessment, development and evaluation (GRADE) criteria. RESULTS: A total of nine articles qualified for inclusion in the systematic review, of which four articles were eligible for meta-analysis. Based on the scoring on NOS, majority of the included studies were found to be of moderate risk of bias. Majority of the studies (n = 6) reported significantly (p < .05) decrease in estimated glomerular filtration rate (eGFR) after imatinib treatment. The risk of developing renal dysfunction (chronic kidney disease or acute kidney injury) was found to be significantly higher in imatinib users as compared to other tyrosine kinase inhibitor (TKI) users with a pooled relative risk of 2.70 (95% CI: 1.49-4.91). Sensitivity analysis also revealed a consistently high risk of renal dysfunction with imatinib use. GRADE criteria revealed low certainty of evidence. CONCLUSION: This meta-analysis found an increased risk of renal dysfunction in imatinib users compared to other TKI users.

Experience with combination of hydroxyurea and low-dose thalidomide in transfusion-dependent beta thalassemia patients.

Hydroxyurea (HU) and thalidomide have been reported to improve clinical and hematological parameters in transfusion-dependent beta thalassemia (TDT). Therefore, we retrospectively analyzed the combination of HU and thalidomide in 140 transplant ineligible TDT, ≥ 10 years old, visiting our thalassemia clinic between October 2014 and November 2019. Responses were defined as maintenance of hemoglobin ≥9gm/dl without transfusion as complete response (CR) and with at least 50% reduction in transfusion burden as partial response (PR). Patients with less than 50% transfusion burden reduction for consecutive 6 months of therapy were defined as non-responders (NR), and treatment was discontinued thereafter. Primary end point was overall response rate (ORR) at last follow-up. At median follow-up of 22.6 (95% CI 16.4-28.7) months, 76 (57.2%) patients achieved CR and 19 (14.3%) achieved PR, accounting to an ORR of 71.5%. Among responders at last follow-up, a significant increase in the post-treatment hemoglobin (0.88±0.37gm/dl, p<0.0001) and drop in serum ferritin (-1490.5ng/ml, p<0.0001) were observed. Median time to CR was 124 (95% CI 75.3-172.6) days. Median longest continuous CR was 791 (95% CI 662.2-919.7) days. Common toxicities observed were sedation (25%), hyperbilirubinemia {(23.57%, grade 3/4 =17 (12.14%)}, and constipation (22.8%). Nearly three-fourth of the patients has responded with majority having CR. Adverse events are a concern; hence, regular close monitoring is a prerequisite.

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies.

BACKGROUND: Data on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce. OBJECTIVE: To study 14-day mortality in patients who received CPT. PATIENTS & METHODS: Retrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed. RESULTS: The median age of the study cohort was 62 years (18-80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2-25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy. CONCLUSIONS: We provide a large series of patients with hematological malignancies and role of CPT in this group.

Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma.

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23-68 years). Median time from diagnosis to transplant was 7 months (3-79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9-144.7 months) and 73.8 months (95% C.I. 57.7-89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p = 0.024), while OS was better with CR/VGPR post-ASCT (p < 0.001) and lenalidomide maintenance therapy (p = 0.009). PFS was affected by CR/VGPR pre-ASCT (p = 0.021), CR/VGPR post-ASCT (p < 0.001), and transplant in first remission (p = 0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p = 0.007) and CR/VGPR response post-ASCT (p = 0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p = 0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p = 0.073). CONCLUSION: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.

Incidence and clinical profile of tuberculosis after allogeneic stem cell transplantation.

BACKGROUND: Patients post allogeneic stem cell transplantation (alloSCT) are expected to be at high risk of tuberculosis (TB) owing to underlying immunosuppression. We conducted a retrospective study in patients post alloSCT for clinical features and factors associated with TB. METHODS: Records of all patients transplanted from January 1, 2012 until December 31, 2015 were reviewed. Diagnosis of TB was considered if Mycobacterium tuberculosis was cultured from clinical samples or acid-fast bacilli (AFB) were demonstrated on histopathology/smears. A presumptive TB diagnosis was considered in the presence of signs and symptoms suggestive of TB with epithelioid cell granulomas, without AFB. RESULTS: In 175 eligible patients, TB was detected in 5 patients (pulmonary = 4, lymph node = 1), with incidence of 2.84% at median of 258 (157-639) days after transplantation. Cumulative incidence rate of TB among the patients undergoing alloSCT was calculated to be 1.9/100 person-years. Median duration of symptoms was 20 days till diagnosis was confirmed. All patients were started on four-drug anti-tubercular therapy (ATT) with clinical/radiological response in all. Two patients developed hepatotoxicity (transaminitis, n = 1; hyperbilirubinemia, n = 1) following ATT. Presence of chronic graft-versus-host disease (GVHD) (P = .008) and steroid-refractory GVHD (P = .001) was found to be significantly associated with TB. CONCLUSION: TB should be suspected in patients with unexplained fever post alloSCT. Active GVHD and ongoing immunosuppression/steroids are possible risk factors. Early diagnosis and treatment can salvage most patients. Hepatotoxicity following ATT is a potential concern.

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.

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.

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.

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.

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.

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.

Role of Cytokines in Chemotherapy-related Cognitive Impairment of Breast Cancer Patients: A Systematic Review.

BACKGROUND: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1ß, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Prevalence of Anemia among Chronic Myeloid Leukemia Patients Treated with Imatinib: A Evidence-based Meta-analysis.

BACKGROUND: Imatinib is one of the tyrosine kinase inhibitors used for the treatment of chronic myeloid leukemia (CML) patients. The exact association of imatinib with anemia in CML patients is still unclear. AIM: The current study aimed to find the prevalence of anemia in chronic myeloid leukemia patients treated with imatinib. METHODS: The relevant articles were searched in PubMed, Google scholar, and Clinical trials registries till 31st July, 2021. The quality of the articles was assessed using the Newcastle-Ottawa Scale. The prevalence rate with 95% CI was calculated using StatsDirect Statistical analysis software V.3. RESULTS: A total of 18 studies containing 3537 patients were found relevant for the analysis. The pooled prevalence of anemia in CML was found to be 34% (95% CI: 23%-46%). However, the heterogeneity among studies was found to be high. CONCLUSION: The monitoring of hemoglobin levels and identifying the cause of anemia are major concerns for the CML patients treated with Imatinib.