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

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

The sensitivity of CD138 immunostaining of bone marrow trephine specimens for quantifying marrow involvement in MGUS and myeloma,including samples with a low percentage of plasma cells

This is a publisher's version of an article published in Haematologica 2006 published by European Hematology Association. This version is reproduced with permission from European Hematology Association. http://www.haematologica.org/Accurate quantification of plasma cells in bone marrow samples is essential for the diagnosis, classification and prognosis of plasma-cell dyscrasias. Published comparisons between aspirate/trephine morphology, flow cytometry and immunohistochemistry are lacking. Bone marrow plasma cells from 100 patients with plasma cell myeloma or monoclonal gammopathy of undetermined significance were quantified by a 500-cell differential count on Romanowsky-stained aspirate slides, flow-cytometry gating of CD38bright+/CD138+cells,hematoxylin and eosin trephine section examination and CD138 trephine immunohistology. The results of quantification by the different methods were compared. Compared to other methods, CD138 trephine immunohistology consistently demonstrated greater plasma-cell infiltration. Immunohistology is the most sensitive method for assessment of plasma-cell infiltration at diagnosis or post-therapy,especially in patients with minimal bone marrow involvement

Study of clinical characteristics, risk factors and outcomes for tuberculosis post allogeneic stem cell transplant: never count it out

Background: Allogeneic stem cell transplant (AlloSCT) recipients remain at a higher risk of developing tuberculosis (TB), especially in endemic populations. We conducted a retrospective study to identify the incidence, clinical presentation, and risk factors for active TB among our alloSCT recipients. Methods: Records of all patients transplanted between 1 January 2012 and 31 July 2020 were reviewed. Patients were followed up for outcome until 30 September 2020. None of the patients received prophylactic anti-tubercular drugs. Proven diagnosis of active TB was considered if Mycobacterium tuberculosis (MTB) was cultured from clinical samples or acid-fast bacilli (AFB) or MTB demonstrated on Ziehl-Neelsen (ZN) staining or histopathology or XPERT MTB, while probable diagnosis of TB was considered if histopathology findings were suggestive of caseation necrosis/epithelioid cell granulomas without any evidence of malignancy or lymphocyte rich exudative effusions (pleural/pericardial) without an alternative cause. Results: Among 381 alloSCT recipients, 15 patients (3.9%) developed TB at median of 246 (74–279) days post AlloSCT, after being symptomatic for a median of 22 (7–60) days, amounting to a cumulative incidence of 4.9%. All patients were started on four-drug anti tubercular therapy, ATT [Rifampicin, Isoniazid, Ethambutol, Pyrazinamide (RHEZ)], of which five patients developed hepatotoxicity at a median of 12 days after start of ATT, leading to drug modification. At last follow up, TB was cured in 13 (86.67%) patients, one succumbed to disease relapse, while others are still on treatment. Age ⩾ 30 years, immunosuppression for graft versus host disease (GvHD) > 6 months, prior use of tyrosine kinase inhibitors (TKI) and chronic GvHD on univariate analysis and immunosuppression for GvHD > 6 months on multivariate analysis were found to be associated with development of TB. Conclusion: A high index of suspicion with timely workup and treatment of TB is the key in AlloSCT recipients, especially in endemic TB populations

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

A tertiary care centre experience with Elranatamab: A report of three cases

Introduction: The introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies has changed the treatment paradigm of multiple myeloma. With the advent of these new therapeutic options, life expectancy has substantially increased for myeloma patients which has led to an increased number of patients with triple-class refractory disease. Thus, there remains an unmet need for effective novel therapies with good tolerability and safety profile. Elranatamab, is the most widely used bispecific antibody currently in the Indian setting. However, it has only been used on a clinical trial basis till now, and real-world data especially in the Indian setting is missing. Here, we present our experience with three cases of multi-line treated relapsed/refractory multiple myeloma on elranatamab monotherapy. Case report: We here discuss three of our patients with triple class refractory multiple myeloma who recieved elranatamab monotherapy. While one of our patient had been switched to fortnightly treatment, two patients were still continuing weekly treatment. The common adverse effects observed were grade 1–2 cytokine release syndrome, cytopenias, CMV reactivation and hypo-gammaglobulinemia. While two of our patients are doing well, one patient had grade 3 neurological toxicity, likely drug related and succumbed. Discussion: B-cell maturation antigen is highly expressed on mature B cells and is critical for the survival and proliferation of plasma cells. It has emerged as a novel target for anti-myeloma therapies in the form of bispecific cell engager, antibody-drug conjugates, and chimeric antigen receptor (CAR) T-cell therapies.The phase II MM3 trial showed a promising efficacy with an ORR of 61% with a CR rate of >35%. With a median follow-up of 14.7 months, the median PFS was not reached and the 15-month PFS rate was 50.9%. While it is too early to comment on long term survival with the monotherapy, we here discuss response of Indian patients in the real world setting. Conclusion: Elranatamab monotherapy could prove to be an efficacious option for the treatment of relapsed /refractory multiple myeloma patients with triple-class refractory disease, with limited therapeutic options. However, patients need to be screened for infectious complications with appropriate prophylaxis and immunoglobulin replacement, if required. Also, a high suspicion is required for the neurological complications of the drug and a longitudinal neuro-cognitive screening is required for the patients