This case report illuminates the pivotal role of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT (Positron emission tomography integrated with computed tomography) scan in diagnosing uncommon and elusive pathologies. Through the detailed exploration of a challenging case, we underscore the significance of this imaging modality in unravelling diagnostic mysteries, guiding clinical decisionmaking, and ultimately improving patient outcomes. This case highlights the importance of considering haematological malignancies in the differential diagnosis of pyrexia of unknown origin (PUO), especially when accompanied by cytopenia and bone abnormalities. PET/CT scan revealed extent of disease involvement, it also guided to determine the site of bone marrow biopsy and to decide treatment protocol as well as in response assessment.

Young children with Hemophilia A (CwHA) are at increased risk of arthropathy and inhibitor formation, thereby warranting prophylaxis at an early age. We studied efficacy and safety of emicizumab prophylaxis in CwHA (severe) without inhibitor. Retrospective analysis was performed in young CwHA (<3 year of age at recruitment) who were started on emicizumab between Sep 2021 to Dec 2023. They were either treatment naïve or minimally treated (≤ 5 exposure days). Standard dose of emicizumab was used. Annualized bleeding rate (ABR) was calculated. Emicizumab trough levels were performed. Thirteen children with median age 16 month (6-35) at start of emicizumab were followed-up for median 24 month (14-46). The cumulative follow-up was 342 month. All children were symptomatic at recruitment with 4/13 CwHA having joint bleeds. Median all bleed ABR decreased from 1.7 to zero post-emicizumab. A total of four adverse events (all grade-1) in three children were noted. Mean emicizumab levels were 23.6±10.5 µg/ml (95

Treatment approaches for aplastic anemia (AA) and inherited bone marrow failure syndromes (IBMFS) have evolved significantly, changing how doctors approach initial treatment, transplant decisions, and research directions. For patients with acquired severe AA (SAA), adding eltrombopag, a drug that stimulates platelet production, to the standard combination of anti-thymocyte globulin and cyclosporine has revolutionized immunosuppressive treatment. This approach speeds up blood cell recovery across all three cell lines and improves complete response rates, with survival rates now exceeding 90

Aplastic anemia (AA) is a rare, potentially life-threatening disorder characterized by immune-mediated destruction of hematopoietic stem cells, resulting in a hypocellular bone marrow and cytopenias. Patients typically present with fatigue, infections, and bleeding due to anemia, neutropenia, and thrombocytopenia. Diagnosis is established by demonstrating bone marrow hypocellularity with cytopenias and is classified using the modified Camitta et al. criteria. Compared to the Western world, AA occurs more frequently in Asian populations and at a relatively younger age at presentation. Acquired AA is primarily immune-mediated, involving cytotoxic T-cell destruction of CD34⁺ stem cells and cytokine-mediated suppression of hematopoiesis. Most cases are idiopathic, while secondary causes include infections, drugs, toxins, radiation, immune disorders, and pregnancy. Diagnosis of acquired AA requires exclusion of inherited bone marrow failure syndromes and screening for paroxysmal nocturnal hemoglobinuria (PNH) clones. Diagnosis of idiopathic AA requires careful exclusion of IBMFS and other causes of pancytopenia through detailed clinical assessment and bone marrow examination. It also involves cytogenetic and molecular studies along with screening for PNH clones. Management depends on disease severity, patient age, and donor availability. Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor remains the preferred curative option in eligible patients, whereas immunosuppressive therapy with anti-thymocyte globulin and cyclosporine, often combined with eltrombopag, is recommended for patients ineligible for HSCT. Supportive care is essential for all the patients. These consensus guidelines provide evidence-based recommendations for the diagnosis and management of AA, including severity classification, evaluation for PNH clones, and exclusion of IBMFS. They also address the diagnostic approach and management principles of IBMFS while outlining contemporary treatment strategies such as immunosuppressive therapy and hematopoietic stem cell transplantation, with an emphasis on data from India and other resource-limited settings

Clinical and biochemical screening is recommended to monitor hepatobiliary late-effects in childhood acute lymphoblastic leukemia survivors (cALLs). Transient elastography (TE) noninvasively evaluates liver fibrosis by measuring liver stiffness (LSM) with good sensitivity. We screened cALLs for high-LSM using TE, comparing them to controls and evaluated risk factors for high-LSM. This case–control study included cALLs who were under 18 years at diagnosis, had completed therapy between 2016 and 2023, and were at least 6-months post-completion of therapy. This study also included 50 age- and sex-matched controls. TE (Fibroscan®) was used for LSM, with cutoff ≥ 5.1 kPa for high-LSM indicating fibrosis, and for controlled attenuation parameter (CAP), with cutoff > 248 dB/m for steatosis. Fifty-eight cALLs with mean (SD) age of 136.58 (58) months at enrollment were analyzed after mean (SD) duration of 27 (8) months post-completion of therapy. High-LSM was observed in 22/58 (37.9

Chemotherapeutic protocols developed in high-income countries do not produce comparable results in low- and lower-middle income countries (LMICs). This study analyzed the treatment outcomes of modified Berlin–Frankfurt–Munster (BFM)-2009 protocol in children with acute lymphoblastic leukemia (ALL) in a tertiary care referral center in Northern India. This retrospective study evaluated the treatment outcomes of children with newly diagnosed ALL treated with the modified BFM-2009 protocol using a risk-stratified approach between July 2018 and Dec 2024 and followed-up till June 2025. One hundred sixty six children with a median (q1, q3) age 51 (31, 78) months were followed-up over a median (range) duration of 36.5 (6-84) months. Patients were categorized as standard-risk (SR, 34

PURPOSEOutcomes in adults age 40 years and older with ALL are inferior to younger patients, with limited real-world data.METHODSThis is a retrospective analysis of adults age 40 years and older with newly diagnosed ALL enrolled in the Hematology Cancer Consortium registry from January 2019 to January 2021. Baseline variables, treatment patterns, response rates, toxicities, and survival were assessed. Overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier methodology.RESULTSOf 349 registered patients, 61.3% (n = 214/349) initiated therapy, while 38.6% (n = 135/349) refused therapy. B-ALL represented 81% of cases (n = 174/214). Berlin-Frankfurt-Münster was used in 61.6% (n = 132/214) and German ALL in 30.3% (n = 65/214). Induction mortality was 18.6% (n = 40/214), mainly infection-related. Complete remission rates were 59.8% among assessed patients (n = 128/214), with minimal residual disease negativity in 45.8% (n = 61/133). Treatment de-escalation due to intolerance occurred in 30.8% (n = 66/214), and 35% (n = 75/214) were lost to follow-up. 3.7% (n = 8) patients underwent allotransplantation. At a median follow-up of 34 months, 3-year OS and EFS rates for the entire cohort were 31% and 29.6%, respectively (n = 214). Median OS and EFS were 13 and 11 months, respectively.CONCLUSIONAdults age 40 years and older with ALL in India have poor outcomes, driven by early mortality, treatment intolerance, and limited access to advanced therapies.

Febrile neutropenia (FN) is a life-threatening emergency in hematological disorders, affecting both benign and malignant diseases. Culture positivityremains low, and empirical antibiotic use increases antimicrobial resistance. Data from resource-limited settings are scarce. This study evaluated the clinical profile, microbiological spectrum, and outcomes of FN among patients with hematological diseases in North India, comparing culture-positive and culture-negative episodes. This prospective, observational study was conducted at a tertiary care hospital between August 2022 and January 2025. Patients aged ≥12 years withhematological disorders fulfilling Infectious Diseases Society of America(IDSA) criteria for FN were included. Clinical data, microbiological results, MASCC scores, and outcomes were analyzed. Empirical therapy followed institutional antibiotic protocols, and supportive interventions included G-CSF and granulocyte transfusion as indicated. Statistical analyses were performedusing R, with significance set at p < 0.05. A total of 148 FN episodes were analyzed; mean age was 38.5 years, and 57

Waldenström macroglobulinemia (WM) is a rare, indolent B-cell chronic lymphoproliferative disorder charactersied by bone marrow infiltration with clonal lymphoplasmacytoid cells and the presence of a monoclonal IgM paraprotein. WM represents 1–2

Introduction Data guiding management of tyrosine kinase inhibitors (TKI) during pregnancy in chronic myeloid leukemia (CML) are limited, especially from low- and middle-income countries (LMICs). This study was performed to describe real world outcomes in patients with pregnancy on TKIs for CML. Methodology This retrospective, multicenter study (IMPACT-CML: Indian Multicentric Pregnancy and Chronic Myeloid Leukemia Outcomes Tracking) was conducted by the Hematology Cancer Consortium India CML working group. Women of childbearing age who were on follow up between January 2017 to June 2025 and had a pregnancy while on TKIs or were diagnosed with CML during pregnancy were screened for inclusion. The primary objective was to describe obstetric outcomes, TKI discontinuation, maintenance of major molecular response (MMR) post-pregnancy and pregnancy related complications. Results A total of 478 women were screened, of whom 50 women with a median age of 25 years (IQR 22-28) were included. At the time of conception, 32/50 (64%) were already on TKIs and only 14/50 (28%) pregnancies were planned. Most women (N=45, 90%) were on Imatinib, and the rest on Dasatinib. For most women, this was the first pregnancy after the diagnosis of CML (N=32, 76.2%), ten had a previous pregnancy and data was unavailable for eight. Among 10 women with a prior pregnancy after diagnosis of CML, 6 (60%) had live births, 3 (30%) underwent medical termination (MTP), and 1 had intrauterine death (IUD). Among planned pregnancies (n=14), TKIs were discontinued by 11 (78.6%), with 7(63%) stopping pre-confirmation and 4 (36%) post confirmation of pregnancy. TKI discontinuation was further documented in 12 women during the first trimester, 11 during the second, and 8 during the third, with most stoppages lasting >2 months (92.3%, 91.7%, and 80%, respectively) in each trimester. An overlap with planned cases was not separately defined. Five patients were transitioned to interferon prior to or during pregnancy. Baseline values of BCR::ABL International Scale (IS) (within six months of pregnancy) were available for 33/50 (66%), with a median value of 0.14% (IQR 0.01–0.75), of whom 15 (45.5%) were in MMR or better. Sequential values were available for 13 patients in the first trimester (median 0.25%, Range 0-35), 13 in the second (median 0.26%, Range 0-10), and 9 in the third (median 0.16%, Range 0.01 to 2.09). Pregnancy outcomes were available for 43 women, of whom 25/43 (58.13%) had a live birth (20 term deliveries, 5 preterm) with median birth weight of 2.50 kg (IQR 1.85–2.95, Range 1.12 to 3.50 Kg). Medical termination of pregnancy was opted by 13 patients (13/43, 30.2%), of which 9 (9/13, 69%) were physician advised. One instance each of pregnancy induced hypertension and post-partum hemorrhage were documented. Median gestational age at delivery was 36.5 weeks (IQR 15–37), including term births and terminations. Among patients who remained on TKIs throughout the first trimester (n=35/47 [74.4%]), excluding 3 without outcome data), most (n=18, 51%) achieved term or pre-term delivery, 13 (37%) underwent MTP and 5 (10%) had spontaneous abortions. No congenital malformations were reported in live births, including those who continued TKIs through the first trimester. Post-pregnancy molecular data were reported in 23/50 (46%) patients, with median BCR::ABL IS value of 0.11% (0.01–0.70), with 11 (47.8%) in MMR. There was no statistically significant association between TKI discontinuation and post-pregnancy BCR::ABL IS levels (p=0.2368). Preterm delivery was significantly correlated with unplanned pregnancy (p=0.016) and lack of molecular testing before conception (p=0.024). After a median follow-up of 74.07 months (IQR 41.11–140.70) from CML diagnosis, all patients were alive. Molecular data were available for 48/50 (96%), with median BCR::ABL IS value of 0.01 (IQR 0.00–1.17). Conclusions In the first Indian multicentric data describing pregnancy outcomes in women with CML, we observe a high frequency of healthy live births despite early trimester TKI exposure and preserved long term disease control. Rates of spontaneous abortions were not higher than published data in the general population, highlighting the potential to reduce physician-advised MTPs in this setting. Our data indicates potentially safe outcomes in pregnant women with CML with pre-conception planning and subsequent monitoring.

Background : Talicabtagene autoleucel (Tali-cel), a second-generation, humanized CAR-T cell therapy targeting CD19, was approved in India in October 2023 for the treatment of relapsed or refractory (r/r) B-cell malignancies. This report presents real-world data on its clinical effectiveness, safety profile, and healthcare resource requirements in patients with r/r B-cell non-Hodgkin's lymphoma (B-NHL) treated across multiple centers in India. Methodology: We performed a retrospective review of patients aged ≥15 years with r/r B-NHL who received Tali-cel as standard-of-care (SOC). Following lymphodepleting chemotherapy, patients were infused with ≥5×10⁶ CAR-T cells/kg in a single dose. Bridging therapy was administered at the treating physician's discretion. Response was evaluated using PET-CT or CT imaging according to Lugano 2014 criteria at regular intervals typically at day 28, month 3(M3), month 6(M6), month 9(M9), month 12(M12) and annually for 5 years. Adverse events of interest—including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell–associated hemophagocytic syndrome (IEC-HS), cytopenias, and hypogammaglobulinemia—were graded using ASTCT guidelines. Additional outcomes such as ICU admission, hospital stay, and mortality were documented. Kaplan–Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Results: From the time of approval until May 2025, 60 treatment centers across India administered Tali-cel for B-NHL. A total of 194 patients underwent leukapheresis, 170 received the CAR-T infusion, and 143 were evaluable for safety and efficacy outcome. The manufacturing success rate was 98% (191/194). Fourteen patients died prior infusion. The median patient age was 56 years (range: 17–83), with males accounting for 64% of the cohort. Most patients had received a median of 2 prior treatment lines (range: 1–7), including polatuzumab (14%), and stem cell transplantation (4%). 23% of the patients had bulky disease (largest lesion ≥ 7cm) at enrollment and 79% received bridging therapy prior to CAR-T cell therapy. Median vein-to-vein time was 30 days (range: 16–124). The overall response rate (ORR) was 75% and 60% and CR rate was 57% and 56%at M1 and M3 respectively. The median duration of follow-up was 5 months (range: 1–19). Six month PFS rates was 56%(95% CI: 48-66), while OS rates were 74%(95% CI: 67-83). Median PFS was 10 months, and median OS was not reached. Most common toxicity was cytopenia with incidence of Grade 3-4 (G3-4) in 71% of the patients. Incidence of CRS was 75% (G3-4: 6%), and ICANS was 11% (G3-4: 3%) of the patients. Hypogammaglobulinemia and IEC-HS were observed in 50% and 17% of patients, respectively. Tocilizumab was administered in 63% patients who developed CRS with median dose of 1 (range 1-3). Vasopressor and Corticosteroids was required only in 6% and 8% respectively. IVIG support was required in 34% patients and anakinra for management of IEC-HS was required 75% respectively. 6% of patients required ICU-level care. The overall median hospital stay was 12 days. Conclusion: This real-world analysis demonstrates that tali-cel is a practical, effective, and well-tolerated treatment option for r/r B-NHL in India. As the first large-scale, multicenter evaluation of this therapy in the Indian healthcare landscape, our findings support its broader implementation across various levels of clinical practice.

Background: In India, access to curative therapies for relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) remains limited due to restricted availability of allogeneic transplants and monoclonal antibodies. Talicabtagene autoleucel (Tali-cel), a CD19-directed humanized CAR-T cell therapy, was recently approved as the first commercial CAR-T therapy in India and is priced at nearly one-tenth the cost of similar U.S. therapies. Early intervention with Tali-cel may reduce treatment-related toxicity and healthcare resource utilization (HCRU), offering an affordable therapeutic option in resource-constrained settings. We present real-world data on the clinical outcomes, safety, and HCRU associated with early vs. late use of Tali-cel. Methods: This retrospective real-world study included 118 patients with r/r B-ALL who received Tali-cel between November 2023 and May 2025 in India. Patients were stratified based on timing of relapse: early treatment (first or second relapse) vs. late treatment (≥ third line failure). Clinical efficacy was assessed by bone marrow morphology and flow cytometry, per NCCN guidelines v2.2024.Disease response was assessed at regular intervals typically at day 28, month 3(M3), month 6(M6), month 9(M9), month 12(M12) and annually for 5 years. Progression-free survival (PFS) was analysed using Kaplan–Meier method. Safety outcomes included adverse events of special interest such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell–associated hemophagocytic syndrome (IEC-HS), hypogammaglobulinemia, and cytopenias —graded per ASTCT criteria. HCRU was accessed by hospital length of stay, ICU admission, clinical management of toxicities. Cost estimates were derived from institutional billing and resource use models of public sector tertiary cancer centre in India. Results: A total of 118 patients with r/r B-ALL received tali-cel, of whom 81 patients were treated in early treatment (defined as first or second relapse) and 37 patients in late treatment (≥ third line). Baseline characteristics were well balanced between groups: median age (24 vs. 26 years), male gender (78% vs. 74%), and disease burden at apheresis (3% vs. 2% blasts). Patients treated in early treatment demonstrated significantly better clinical outcomes. The patients with early treatment had overall response rates (ORR) of 93% and 86% at M1 and M3 post tali-cel infusion; in contrast to the late treatment group with 81% and 56% respectively. Estimated PFS at 6 months favoured early treatment (88% vs. 70%), indicating more chances of durable disease control. Early treatment was associated with fewer severe adverse events. ICANS occured in occurred in 6% of early vs. 16% of late patients; with Grade 3-4 incidence in 3% vs. 8%, respectively. Rates of cytopenias were comparable (69% in both groups), as were Grade 3-4 CRS (7% vs. 8%), IEC-HS (22% vs. 18%) and hypogammaglobulinemia (52% vs. 46%). Early treatment significantly reduced health care resource use. Median hospital stay was 6 days in early vs. 12 days in late group (p<0.01). ICU admissions were markedly lower (3% vs. 22%, p<0.01) and ICU stay shorter (median 2 vs. 9 days, p<0.05). Supportive care requirements were reduced: vasopressor use (5% vs. 8%) and corticosteroids (7% vs. 39%, p<0.01) were both lower with early use. Utilization of tocilizumab (72% vs. 62%), anakinra (26% vs. 24%), and IVIG (49% vs. 54%) was similar between groups, reflecting consistent supportive management. Cost modelling revealed a 60% reduction in median hospitalization costs for early-relapse patients, driven by shorter hospital stay, less ICU need, and fewer high-grade toxicities requiring intensive management. Conclusion: In this real-world cohort, patients with early relapse r/r B-ALL treated with tali-cel achieved more durable responses, with higher remission rates and longer progression-free survival compared to those treated later in the disease course. Importantly, early use was associated with lower toxicity, reduced healthcare resource utilization, and a significant reduction in overall cost of care. These findings suggest that early intervention with Tali-cel represents a potentially cost-effective treatment strategy, especially in resource-limited healthcare settings.

Background Multiple Myeloma (MM) is a clonal plasma cell disorder, and autologous hematopoietic stem cell transplantation (HSCT) remains a cornerstone of treatment. This study evaluates the clinical outcomes, prognostic factors, and survival benefits of autologous HSCT in Indian MM patients. Methods A retrospective observational study was conducted across five tertiary care centers from 2010 to 2024. Patients who underwent autologous HSCT were analyzed for baseline characteristics, transplant-related complications, response rates, event-free survival (EFS), and overall survival (OS). Statistical analyses were performed using Kaplan-Meier survival estimates and multivariate regression modeling. Results A total of 365 patients (mean age: 54 ± 10.3 years) underwent autologous HSCT. The day +100 post-transplant response showed 77% achieving complete remission (CR) or better. The 1-year, 2-year, and 5-year OS were 91%, 85%, and 72%, respectively. The median OS was not reached at a median follow-up of 602 days. Transplant-related mortality (TRM) was 3.56%. Key prognostic factors influencing survival included pre-transplant response status, CD34+ cell dose, and ISS stage. Conclusion Autologous HSCT is a safe, effective, and financially viable option for MM patients in resource-limited settings. Improved supportive care and patient selection have contributed to favorable long-term outcomes. Further prospective studies are warranted to validate these findings.

Cytomegalovirus (CMV) infection in immunocompromised patients can cause significant morbidity and mortality. Early recognition and treatment helps to improve outcome. We present a case of postrenal transplant CMV infection causing both upper and lower gastrointestinal infection and symptoms. Patient developed significant co-morbidity which required multiple hospital admissions and therapeutic interventions.

ObjectiveTo determine the body composition in childhood acute lymphoblastic leukemia survivors (cALLS) using dual-energy x-ray absorptiometry (DEXA) and correlate the same with mid-upper-arm circumference (MUAC) and triceps-skin-fold thickness (TSFT). MethodsA cross-sectional study was undertaken to assess body composition in cALLS aged >7 years. Patients who were lost to follow-up after completion of therapy, had relapsed acute lymphoblastic leukemia (ALL), undergone hematopoietic stem cell transplantation and those with neurological disabilities/syndromic diagnosis were excluded. Prevalence of high-adiposity (body fat % > 85th centile), sarcopenia (lean body mass < 5th centile) and sarcopenic obesity (positive fat mass index z-score with negative fat-free mass index z-score); and demographic, therapy-related and endocrine factors were noted. ResultsFifty-nine cALLS survivors with a median (IQR) age of 66 (38, 91) months at diagnosis were analyzed. At a median (IQR) duration of 14 (3, 43) months following completion of therapy, 36 children (61%) had deranged body composition; high adiposity (n = 28; 47%), sarcopenia (n = 20; 34%), sarcopenic obesity (n = 9; 15%). Metabolic syndrome was seen in 7 (12%). Survivors with lower mean-age at diagnosis and at enrolment had high-adiposity levels and sarcopenia. Sarcopenia was seen more commonly in females, pre-pubertal children and survivors with a lower mean-interval from therapy completion. Obesity, sarcopenia and sarcopenic obesity were not significantly associated with the type of ALL, steroid dose and cranial-irradiation. High leptin levels were seen in survivors with obesity and sarcopenic obesity. MUAC and TSFT correlated well with DEXA-generated markers. ConclusionThe prevalence of deranged body composition in cALLs from a single centre in Northern India was high, indicating need for early and frequent screening. MUAC and TSFT are reliable surrogate measures for body composition.

Immune thrombocytopenia (ITP) is an autoimmune disorder and there is a need to further enhance the understanding of the pathogenesis of ITP and look for newer targets for better treatment and outcome. We aimed to estimate the MFI (Mean Fluorescence Intensity) of CD11a on lymphocytes and correlate with the disease severity, and response to therapy in ITP. This case-control study was conducted at a tertiary care center in Northern Bharat. The patients aged more than 12 years with a diagnosis of ITP, confirmed as per ASH guidelines, were included in the study. Healthy volunteers were included as controls for the study. Statistical analysis was done using StatsModels 0.13.5 package of Python 3.11. Paired t test was used to compare pre and post treatment means of level of CD11a in patients who responded. The present study was conducted among 66 cases (ITP) and 36 controls. The result showed low MFI of the CD11a on CD19, CD3, and CD4 in ITP as compared to the healthy control, especially the statistically significant low MFI on CD3 cells (p < 0.05). Further, CD11a MFI showed a linear relationship with platelet count and there was a statistically significant reduction in CD11a MFI on CD3 cells in severe ITP as defined by WHO Bleeding Grade 3 when compared with WHO Bleeding Grade 1 and 2 (p < 0.05). Though statistically insignificant, the baseline MFI of the CD11a on CD4 was lower but on CD19, and CD3 it was higher in patients who were refractory to therapy. On follow-up (after treatment), the mean MFI of the CD11a on CD19, CD4, and CD3 was lower in refractory cases as compared to the non-refractory cases. The comparison of the baseline and after-treatment MFI of CD11a on CD19, CD3, and CD4 showed a slight increase. When stratified with refractory status: The CD11a on CD19 increased after treatment in both the groups however, the increase was higher in the non-refractory group. We conclude that the CD11a has a linear relationship with platelet count and there is statistically significant low MFI of CD11a on CD3 cells in severe ITP characterized by WHO Bleeding Grade 3. While on therapy, the lack of increase in CD11a MFI predicts poor response to the therapy.

Introduction: Dual negativity for cluster designation (CD) 34 and human leukocyte antigen (HLA)-DR antigen in leukemia panel is an important finding in clinical practice. The combination of this finding though seen classically in acute promyelocytic leukemia (APL) is not specific to it but can be seen in many other myeloid leukemias like the ones associated with nucleophosmin 1 (NPM1) or FMS-related tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) abnormalities. It is important to identify APL from non-APL leukemia as treatment and prognosis vary. Aims and Objectives: We analyzed CD 34 and HLA-DR dual-negative acute myeloid leukemia (AML) cases presented to us over 2.5 years (26 cases) and segregated them into APL and non-APL groups to study their morphological/flow cytometric and cytogenetic profile and correlation with treatment response. Materials and Methods: It was a prospective study including all newly diagnosed AMLs showing CD 34 and HLA-DR dual negativity in flow cytometry profile. Cases in which complete information/cytogenetics/molecular profile were not available, were excluded from the study. The patients were followed up till the end of induction to look for morphological response to induction therapy. The clinical and treatment records were pulled out from the patient database after ethical committee clearance. Results: A total of 139 new AML cases were encountered during the study period out of which 28 (20%) were found to be dual negative for CD34 and HLA-DR. The non-APL group showed higher mean age, TLC at baseline, variable morphology, and more number of aberrant expression on flow cytometry profile. No significant difference was noted in terms of gender, presence of hepatosplenomegaly, DIC as complication, or percentage of blasts/blasts equivalent at baseline. Our study found that while all APL patients had PML-RARA, the associated molecular abnormalities were much lesser as compared to the non-APL group which showed a variety of abnormalities such as NPM1, FLT3, RAS mutation, and mutations involving epigenetic modifiers. The response rate to induction therapy was significantly lower in the non-APL group as compared to the APL group. Conclusion: The non-APL myeloid leukemia which is dual negative is commonly found to be associated with cup-shaped morphology, NPM, or FLT3-ITD mutation along with other abnormalities. These patients were older in age, showed higher TLC and higher blast counts, associated with poorer response to induction therapy as compared to the APL group.

Background Chronic Myeloid Leukemia (CML) is primarily treated with Tyrosine Kinase Inhibitors (TKIs), with Imatinib (IM) being the first-line therapy for over two decades. While its efficacy and long-term survival benefits are well established, the long-term impact on renal function remains inadequately studied, especially in Indian patients. Previous reports suggest a progressive decline in estimated glomerular filtration rate (eGFR) in patients on prolonged IM therapy, raising concerns regarding chronic kidney disease (CKD) risk in this population. The KITE Study (Kidney Impact of Ten-Year Exposure) aims to evaluate the renal function of CML patients on IM for over 10 years.Methods This multicentric retrospective analysis from 9 contributing hematology centers, all part of the Hematology Cancer Consortium (HCC), a non-government registry from India, evaluated baseline and current biochemical and demographic data and calculated eGFR at two time points in patients who had received IM as first-line TKI for CML-CP for a minimum of 10 continuous years. Other variables analyzed included molecular remission status and comorbidities (diabetes mellitus [DM], hypertension [HTN], and coronary artery disease [CAD]). Patients with pre-existing CKD, TKI switching, HSCT, or enrollment in TFR trials were excluded. eGFR was calculated at baseline and last follow-up using the CKD-EPI formula and expressed in ml/min.Results Total of 223 patients aged ≥18 years were analyzed. Median age at diagnosis was 40 years (18-81), 148 (66.4%%) were males and median IM exposure was 13 years (range 10–25). At final follow-up, 89% of patients were in major molecular remission (MMR). The prevalence of comorbidities was: DM 5.8%, HTN 9.5%, and CAD 1.8%. - Median eGFR declined from 103 ml/min (baseline) to 89.5 ml/min (follow-up) - This represents a median reduction of 14 ml/min over 13 years, equivalent to ~1.08 ml/min/year. - Female patients had a significantly lower median GFR decline compared to males (8 vs. 16 ml/min; p = 0.0213) - No statistically significant difference in GFR decline was observed with respect to age group (≤30 vs. >30 years; p = 0.9766), MMR status (p = 0.8402), HTN (p = 0.6359), DM (p = 0.1644), or CAD (p = 0.5581).Discussion While hematological, gastrointestinal, and dermatological toxicities of IM are well recognized and monitored due to their impact on tolerance and compliance, renal function deterioration with long-term IM exposure is often under-recognized. In contrast to the ~0.32 ml/min/year decline observed in age-matched general populations, this study reveals a 3-fold greater decline in eGFR with prolonged IM use. Importantly, male sex was associated with a significantly greater decline in GFR, highlighting the need for sex-specific renal monitoring strategies. To the best of our knowledge, this is the largest study to date evaluating renal function decline in long-term IM-exposed CML patients. These findings underscore the importance of routine renal monitoring and reconsideration of treatment goals such as TFR in long-term IM-treated patients. Further studies comparing other TKIs are warranted to guide TKI selection, especially in patients unable to achieve TFR.