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Background: Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post‐AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. Materials and methods: We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient‐specific, disease‐specific, and transplant‐specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen‐related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. Results: Ninety‐five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33–68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4–144). Eighty‐nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile‐associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9–14) and 12 days (range 9–23), respectively. The median duration of hospital stay was 16 days (range 9–29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant‐related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression‐free survival of the study population at 5 years were 72.7% and 64.8%, respectively. Conclusion: This study shows that the incidence of infections and TRM are higher in MM patients from lower‐middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis. [ABSTRACT FROM AUTHOR]

This article discusses the trends in autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed multiple myeloma over the past three decades. The study found that the utilization rates of ASCT have increased in resource-rich regions, while treatment-related mortality (TRM) rates have decreased. However, in resource-challenged regions like India, ASCT TRM rates remain high. The article suggests that centers in resource-challenged settings should carefully consider the pros and cons of upfront ASCT and regularly assess TRM rates until they decrease to 1% or lower. [Extracted from the article]

There is no comparative health-related quality of life (HR-QoL) data of transplant eligible (TE) multiple myeloma (MM) patients undergoing early autologous stem cell transplantation (ASCT) and those without in the era of novel drugs. This study prospectively evaluated the serial HR-QoL in TE-MM using the EORTC QLQ-C30 and MY20 questionnaires. Barring the transient worsening in QoL one-month after ASCT, there was a comparable improvement in most QoL domains in both early-ASCT and no-early ASCT cohorts. Post-early-ASCT patients had higher global health scores (71.9 vs. 60.8, p <.05) than no-early ASCT at 12-months. Patients belonging to lower socioeconomic status (SES) were more likely not to undergo ASCT than middle-high SES patients (38.6% vs. 74.5%, p <.05). While age, gender had no impact on QoL, performance status, staging, and induction therapy impacted QoL. This study shows that early ASCT maintains QoL and should be encouraged in all TE-MM patients. [ABSTRACT FROM AUTHOR]

Lenalidomide maintenance after frontline chemo-immunotherapy (CIT) in chronic lymphocytic leukemia (CLL) has not been standard due to the availability of novel therapies, though these remain out of reach for most in low-middle income countries. This single-center, open-label study randomized CLL patients (non-deletion 17p) after frontline therapy to lenalidomide maintenance (dose-escalated 2.5–10mg, 20/28 days per cycle for six months) or observation (2:1 allocation). Forty patients were included over 2018–2020. At a median follow-up of 22 months, median progression-free survival (PFS) with lenalidomide was not significantly different than observation (26 vs. 18 months, p = 0.4). Patients with minimal residual disease >10−2 had a trend toward better PFS with lenalidomide (19 vs. 7 months, p = 0.07). Grade 3 neutropenia was seen in 16.7% of patients on lenalidomide. Quality of life was comparable between the two arms. Low dose, fixed duration lenalidomide maintenance is not an effective strategy after frontline CIT in CLL. [ABSTRACT FROM AUTHOR]

The need for prognostication in chronic lymphocytic leukemia (CLL) is felt due to the heterogeneous clinical course of CLL, to counsel the patients, tailor follow-up, and to guide treatment decisions. There were predominantly CLL patients on wait and watch in our cohort compared to patients in the CLL-IPI cohort (48% I vs. i 19%, I p i <.0001). The CLL-IPI incorporating comprehensive patient data from prospective clinical trials were proposed in 2016 by a group of international CLL experts to be the standard of care in reporting of clinical trials and clinical practice. [Extracted from the article]

The role of regulatory T-cells (Treg) and Th17 cells in the progression of multiple myeloma has been unclear. There are conflicting reports of the Treg and Th17 frequency being increased, decreased, and unchanged as compared with controls. In this study, we sought to characterize the T-cell subsets including Treg function in both blood and marrow compartments of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). The Treg/Th17 ratio is skewed toward the suppressive phenotype in MGUS and MM. There are more activated and memory Tregs in the myeloma marrow. Although the myeloma Tregs are functional, they are less suppressive than Tregs in chronic lymphocytic leukemia where they drive disease progression. None of the T-cell subsets were found to have a clinical correlation with time to progression in MGUS or progression-free survival in myeloma. Tregs are important but unlikely major players in the progression of MGUS to MM. [ABSTRACT FROM AUTHOR]

The reasons for progression and autoimmune cytopenias (AIC) in chronic lymphocytic leukemia (CLL) are not entirely clear, with previous studies suggesting a role for regulatory T-cells (Treg). In this study we prospectively studied Treg (CD3 + CD4+ CD25highCD127low), interleukin-10 (IL-10) producing Treg and T-helper 17 (Th17) (CD3 + CD4+ IL-17+) cells in 40 treatment-naive patients with CLL. The percentage of Th17 and not Treg cells was significantly higher in the AIC cohort than in those without AIC (p< 0.0001). The Treg:Th17 ratio was skewed in favor of Th17 in the AIC cohort (p= 0.02). Th17 cells are responsible for AIC of CLL. Analysis of lymph-node aspirates showed that the percentage of Treg and IL-10 expression in Treg and not Th17 was significantly higher than in peripheral blood (p< 0.01). Treg cells play a major role in the microenvironment where disease progression occurs. This shows the importance of maintaining the Treg:Th17 equilibrium, for imbalance leads to CLL progression or AIC. [ABSTRACT FROM PUBLISHER]

Regulatory T-cells (Tregs) have been shown to be important for the balance of autoimmunity and oncogenesis. Tregs have a protective role in autoimmune diseases and conversely promote oncogenesis. Chronic lymphocytic leukemia (CLL) is unique in being at the cross-roads of oncogenesis and autoimmunity. We studied Tregs, defined as CD4+CD25highCD127lowFOXP3+, in 32 treatment-naive patients with CLL. Our study shows that patients with CLL had a higher absolute Treg count than the control group ( p < 0.001). A progressive increase of Tregs was noted in advanced stages of the disease ( p < 0.001). The increase in absolute Treg count is more significant than the increase in percentage Tregs. The absolute Treg count appears to be more important in disease pathogenesis. The absolute Treg count was significantly higher in those patients having autoimmune cytopenias. There was an inverse correlation between lymphocyte doubling time and absolute Treg count ( p = 0.03). The absolute Treg count may be used as a prognostic marker in CLL. [ABSTRACT FROM AUTHOR]

AbstractThis study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009–2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management. [ABSTRACT FROM AUTHOR]

Background: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). Aim: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. Methods: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. Results: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. Conclusion: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the outcomes of splenectomy versus cladribine for the treatment of hairy cell leukemia in settings with limited resources. Researchers evaluated the cases of 43 patients at an Indian hospital between 2001 and 2012. They cautiously concluded that splenectomy may still be considered as an alternative to cladribine for hairy cell leukemia in countries with limited resources.

Symptomatic hyperviscosity is an oncologic emergency which is suspected when patients with certain hematogical malignancies present with neurological symptoms. Hyperviscosity syndrome is a rare clinical manifestation in multiple myeloma. We describe a case of a 61 year old lady who developed pulmonary infiltrates after being diagnosed with multiple myeloma. Treated as an infection with antibiotics and intravenous immunoglobulin, she had neurological symptoms which suggested the possibility of hyperviscosity syndrome. The patient received one session of plasma exchange with which her symptoms improved and chest infiltrates resolved (high output pulmonary edema). The case highlights a known but rare manifestation of multiple myeloma, which when diagnosed and treated quickly can have gratifying results. [ABSTRACT FROM AUTHOR]

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/μL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/μL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/μL (range 1000–19000/μL) and 8000/μL (range 1000–19000/μL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP. [ABSTRACT FROM AUTHOR]

Though the chronic lymphocytic leukaemia (CLL) management options in India are still limited compared to the novel drug options in resource-rich settings, the availability of less costly generics and the government health insurance scheme has enabled many patients to access the newer drugs in India. The current study compared the cost-effectiveness and cost-utility of existing initial management options for the progression-free survival (PFS) time horizon from the patient's perspective. A two-health-state, PFS and progressive disease, Markov model was assumed for three regimens (generics): ibrutinib monotherapy, bendamustine-rituximab (B-R), and rituximab-chlorambucil (RClb) used as the frontline treatment of CLL patients in India. All costs, utilization of services, and consequences data during the PFS period were collected from interviewing patients during follow-up visits. The transition probability (TP) and average PFS information were obtained from landmark published studies. EQ-5D-5L questionnaires were utilized to assess the quality of life (QoL). Quality-adjusted life years (QALY) were measured during the PFS period. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were studied. Upon analysis, the entire monetary expense during the PFS time was ₹1581964 with ibrutinib, ₹171434 with B-R, and ₹91997 with RClb treatment arm. Pooled PFS and QALY gain was 10.33 and 8.28 years for ibrutinib, 4.08 and 3.53 years for the B-R regimen, and 1.33 and 1.23 years in RClb arms, respectively. Ibrutinib's ICER and ICUR were ₹214587.32 per PFS year gain and ₹282384.86 per QALY gain when assessed against the B-R regimen. Ibrutinib also performed better in ICER and ICUR against the RClb arm with ₹157014.29 per PFS year gain and ₹200413.6 per QALY gain. In conclusion, generic ibrutinib is a cost-effective initial line of management compared to other commonly used treatment regimes in resource-limited settings. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APML) patients are prone to thrombosis. However, thrombosis at presentation is rare in APML. Our patient presented with thrombosis and cytopenia, and the clinical diagnosis was of paroxysmal nocturnal hemoglobinuria. However, subsequent peripheral blood smear and bone marrow study confirmed the diagnosis of APML. The patient was successfully managed with anticoagulation, arsenic trioxide, and all-trans retinoic acid. [ABSTRACT FROM AUTHOR]

Thirty-seven patients were alive at the last follow-up, 13 had died (two dementia-related causes, one pneumonia, one warfarin-related bleeding, one ovarian cancer, eight because of unknown causes); no patient died due to CLL progression. Of the five patients initially categorized as in partial SR, three have subsequently converted to SR, one remains in partial SR and in one patient who achieved a partial SR after 19 years from diagnosis the lymphocyte count started to increase five years later. Of the four patients in stage B/II at diagnosis, two converted to A/0 and one to A/I. In the five patients with a partial SR, the median lymphocyte count at regression was 6.3 × 10 SP 9 sp /L, with a median lymphocyte decrease of 75.1% (69-89%), and at the last follow-up a median lymphocyte count of 5.6 × 10 SP 9 sp /L (5.3-11.8) (Figure 1). [Extracted from the article]

Summary: Arsenic trioxide (ATO) and all‐trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high‐risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate‐ and high‐risk disease received a further 2 years of maintenance with ATRA, 6‐mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow‐up. The mean (SD) estimated 5‐year event‐free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5‐year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long‐term outcomes in the real‐world setting. [ABSTRACT FROM AUTHOR]

Background & objectives: Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukaemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment-free remission (TFR) with generic imatinib. This study attempted to determine the feasibility and efficacy of TFR in patients on generic Imatinib. Methods: In this single-centre prospective Generic Imatinib-Free Trial-in-CML-CP study, twenty six patients on generic imatinib for ≥3 yr and in sustained deep molecular response (BCR ABLIS ≤0.01% for more than two years) were included. After treatment discontinuation, patients were monitored with complete blood count and BCR ABLIS by real-time quantitative PCR monthly for one year and three monthly thereafter. Generic imatinib was restarted at single documented loss of major molecular response (BCR ABLIS>0.1%). Results: At a median follow up of 33 months (interquartile range 18.7-35), 42.3 per cent patients (n=11) continued to be in TFR. Estimated TFR at one year was 44 per cent. All patients restarted on generic imatinib regained major molecular response. On multivariate analysis, attainment of molecularly undetectable leukaemia (>MR5) prior to TFR was predictive of TFR [P=0.022, HR 0.284 (0.096-0.837)]. Interpretation & conclusions: The study adds to the growing literature that generic imatinib is effective and can be safely discontinued in CML-CP patients who are in deep molecular remission. [ABSTRACT FROM AUTHOR]

Pharmacokinetics of cyclophosphamide has been explored to optimize conditioning dosing. We hypothesized that post-transplant cyclophosphamide (PTCy) metabolite carboxy-ethyl phosphoramide mustard (CEPM) pharmacokinetics might impact haploidentical transplantation (haplo-HCT) outcomes. CEPM area under the curve (AUC0–48) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUC0–48 in a cohort of 30 patients was 14.2 (14) mg·hr/L. The incidence of severe chronic graft-versus-host disease (GVHD) (73% vs. 11%, p = 0.02), and GVHD-/relapse-free survival (GRFS) was significantly inferior in the CEPM AUC0–48 < 14 mg·hr/L group (54 days vs. 344 days, p = 0.02). There was, however, no difference in grade III-IV acute GVHD (38% vs. 14%, p = 0.12) and overall survival (295 days vs. not reached, p = 0.2). CEPM AUC0–48, is associated with severe chronic GVHD and GRFS post-haplo-HCT in this exploratory study. There is scope for personalizing day + 4 PTCy dose based on day + 3 CEPM AUC0–8. [ABSTRACT FROM AUTHOR]

The article presents a case report of a young patient with ulcerative colitis who developed gingival overgrowth due to azathioprine-induced pancytopenia. It mentions that the underlying mechanism involves a genetic variant that affects cation flux and folate uptake, leading to dysfunctional connective tissue degradation. Topics discussed include the adverse effects of azathioprine, the role of genetic factors in drug-induced toxicity, and the management of gingival overgrowth in the patient.

Background: Immunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real‐world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders. Materials and Methods: A retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure. Results: Immunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with <10% PCs and 318/352 (90.3%) with ≥10% PCs in BM aspirate; P =.003). Among cases with unsuccessful IMCS (<10% PCs; n = 21 and ≥10% PCs; n = 34), an alternate source could be used successfully in 34 (62%) patients and includes air‐dried trephine biopsy imprint smears (n = 28) with aggregates or sheets of PCs, fine‐needle aspiration smears/biopsy from plasmacytoma (n = 5), and ascitic fluid (n = 1). 284/395 (71.9%) patients with successful IMCS and all 34 cases with an alternate source of PCs showed at least one cytogenetic abnormality on four‐probe FISH. Conclusion: Variations in the sample quality together with significant variation in the number of PCs between BM aspirate and the trephine biopsy imprint smears/biopsy reduce the success rate of IMCS in a real‐world scenario and necessitate utilization of patient‐specific alternate sources of PCs like a trephine biopsy imprint or cytology smears from extramedullary sources for successful FISH testing in PC neoplasms. [ABSTRACT FROM AUTHOR]

The article focuses on a study which described the safety and efficacy of high-dose hydroxyurea (HDH) for cytoreduction in acute promyelocytic leukemia (APL). Ultra-high-risk patients with APL were analyzed between 2016 and 2021. It was observed that study participants who received HDH has lower early mortality and that none of them developed mucositis. Overall survival of the patients were compared using the Kaplan-Meier technique.

Concerns persist about venetoclax’s long-term safety in larger populations, with limited evidence of infrequent and delayed adverse events (AEs). The study integrated safety data on venetoclax in leukemia patients from randomized controlled trials (RCTs) and FDA adverse event monitoring system (FAERS). We systematically reviewed RCTs reporting safety outcomes of venetoclax in adult leukemia patients of any gender, either monotherapy or in combination, applying advanced search on databases like PubMed, EMBASE, and ClinicalTrial.gov. The quality assessment was done using the Cochrane Risk of Bias Tool. We utilized a random effect meta-analysis to calculate risk ratio (RR) with 95% confidence intervals (CI). The Open Vigil 2.1 MedDRAv24 was used to search the FAERS database, with data available until September 2023. The disproportionality was calculated using the proportional reporting ratio and the reporting odds ratio. The study protocol for meta-analysis was registered with PROSPERO; CRD42022378006. For the safety meta-analysis, seven RCTs with available AEs were examined. A total of 942 AEs were found associated with the venetoclax group; 79% of them were in grade three or above. Venetoclax significantly increased the risk of neutropenia grade three or above (RR = 1.34, 95% CI: 1.10–1.64, p: 0.0033) compared with the control group. In FAERS, 26,436 patients were reported with AEs associated with venetoclax. Significant signal scores were observed in hematological, cardiac, vascular, and gastrointestinal disorders. 11 out of 30 generated signals, failed to meet the signal criteria upon refinement. The current study updated and improved the safety profile of venetoclax in the post-marketing period, assisting in risk evaluation and mitigation for the best possible patient health care. [ABSTRACT FROM AUTHOR]

Dear Editor, Tyrosine kinase inhibitors (TKI) have significantly improved the outcome and survival in patients of leukemia. However, these agents are frequently associated with mucocutaneous adverse effects including, but not limited to, cutaneous rash, xerosis, pruritus, alopecia, and stomatitis.[[1]] Herein, we report a case of generalized lamellar ichthyosis-like rash in the setting of ponatinib, a third-generation TKI used for treatment of chronic myeloid leukemia (CML). Phase 2 and 3 clinical trials have shown xerosis, pruritus, and rash to be the most common mucocutaneous adverse effects associated with ponatinib therapy.[3] Other reported cutaneous adverse effects of ponatinib include pityriasis rubra pilaris-like eruption, prominent folliculocentric seborrheic eruption, diffuse ichthyosiform changes, and ichthyosis vulgaris-like eruption.[3], [4], [5] To the best of our knowledge, this is the first report of ponatinib-induced lamellar ichthyosis-like eruption from India. [Extracted from the article]

Richter's transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with unfavorable prognosis. The clinical and laboratory findings of RT are nonspecific and requires histopathological confirmation for the diagnosis.18F-labeled fluoro-2-deoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) has shown higher diagnostic values for the detection of transformation of CLL/SLL to aggressive lymphoma. We present a case of CLL in remission for 6 years presenting with clinical features suggestive of RT.18F-FDG PET/CT done in our case showed liver and lung involvement with no lymphadenopathy, which is an unusual presentation of RT. [ABSTRACT FROM AUTHOR]

Introduction: There is a close association between the use of broad‐spectrum antibiotics, gut microbiome alteration, multidrug resistant (MDR) gram‐negative bacilli (GNB) bacteremia, graft versus host disease (GVHD), and mortality post‐allogeneic hematopoietic cell transplantation (allo‐HCT). This study reports the impact of the high use of carbapenems and colistin and MDR bacteremia pre‐ and post‐HCT on HCT outcomes. Methods: This was a single‐center, partial retrospective, and prospective study from 2016 to 2020. Both pre‐ and post‐HCT antibiotic exposures and blood culture/sensitivity were recorded. MDR GNB was defined as either non‐susceptibility to third‐generation cephalosporin or carbapenems. In the absence of positive cultures, the treating physician escalated antibiotics from third‐generation cephalosporins to carbapenem and/or colistin as per clinical discretion. De‐escalation policy was not strictly enforced. Results: MDR GNB bacteremia was seen in 29 of 76 (38%) of patients peri‐HCT. The utilization rates for carbapenems and colistin was significantly higher in the cohort with MDR GNB bacteremia pre‐HCT (70% vs. 32%, p = 0.002 and 31% vs. 6.4%, p = 0.007, respectively) and post‐HCT (100% vs. 74.5%, p = 0.002, and 55.2% vs. 8.5%, p < 0.0001, respectively). The cohort with MDR GNB bacteremia had significantly more severe acute GVHD at day+100 (45% vs. 17.5%, p = 0.009). The median survival was 204 days compared to not reached in the cohort without any MDR GNB bacteremia (p = 0.005). Conclusion: This study shows pre‐ and post‐HCT MDR GNB bacteremia is associated with an increased risk of severe acute GVHD and mortality. Patients with MDR GNB bacteremia had higher exposure to pre‐ and post‐HCT carbapenems and colistin. [ABSTRACT FROM AUTHOR]

Background: Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain.Methods: We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively.Results: Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn's disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336).Conclusion: NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia. [ABSTRACT FROM AUTHOR]

The overexpression of cytokine receptor-like factor-2 (CRLF2) identified by anti-thymic stromal lymphopoietin receptor/TSLPR flow cytometry (FCM) has been reported as a screening tool for the identification of BCR-ABL1-like B-cell acute lymphoblastic leukemia/B-ALL with CRLF2 re-arrangement. TSLPR expression was studied prospectively in consecutive 478 B-ALLs (≤ 12 years (n = 244); 13–25 years (n = 129); > 25 years (n = 105)) and correlated with various hematological parameters and end-of-induction measurable residual disease (day 29; MRD ≥ 0.01% by 10-color FCM). TSLPR positivity in ≥ 10% leukemic cells was detected in 14.6% (n = 70) of B-ALLs. CRLF2 re-arrangement was detected in eight cases (11.4%) including P2RY8-CRLF2 (n = 6), and IgH-CRLF2 (n = 2) with a median TSLPR positivity of 48.8% and 99% leukemic cells, respectively. Recurrent gene fusions/RGF (BCR-ABL1 (17.1%); ETV6-RUNX1 (4.2%), TCF3-PBX1 (1.4%)), other BCR-ABL1-like chimeric gene fusions/CGFs (PDGFRB-rearrangement (2.9%), IgH-EPOR (1.4%)), CRLF2 extra-copies/hyperdiploidy (17.1%), and IgH translocation without a known partner (10%) were also detected in TSLPR-positive patients. CD20 positivity (52.9% vs 38.5%; p = 0.02) as well as iAMP21 (4.3% vs 0.5%; p = 0.004) was significantly more frequent in TSLPR-positive cases. TSLPR-positive patients did not show a significantly higher MRD, compared to TSLPR-negative cases (37% vs 33%). Increasing the threshold cut-off (from ≥ 10 to > 50% or > 74%) increased the specificity to 88% and 100% respectively in identifying CRLF2 translocation. TSLPR expression is not exclusive for CRLF2 translocations and can be seen with various other RGFs, necessitating their testing before its application in diagnostic algorithms. In patients with high TSLPR positivity (> 50%), the testing may be restricted to CRLF2 aberrancies, while patients with 10–50% TSLPR positivity need to be tested for both CRLF2- and non-CRLF2 BCR-ABL1-like CGFs. [ABSTRACT FROM AUTHOR]

Introduction: The role of pre‐HCT chest high‐resolution computed tomography (HRCT) and serum galactomannan index (GMI) in predicting the post‐allogeneic hematopoietic cell transplant (HCT) invasive pulmonary aspergillosis (IPA) is debatable. Methods: This was a single‐center, prospective study from 2014 to 2019. The primary objective was to study if pre‐HCT chest HRCT and serum GMI predicted IPA post‐HCT. The secondary objective was day +100 mortality. All consecutive, consenting patients of ≥12 years of age undergoing allo‐HCT were included and had pre‐HCT chest HRCT and serum GMI. All patients received mold active antifungal prophylaxis. The EORTC/MSG criteria were used for the diagnosis of IPA. Results: A total of 82 patients with median age 27 years (12‐59 years) were included. The underlying diagnoses included hematological malignancies (79%) and aplastic anemia (21%). Fifteen percent of patients was treated for prior history of probable IPA (>6 weeks before HCT). Pre‐HCT chest HRCT satisfied EORTC clinical criteria in 24% patients. Serum GMI ≥0.5 was seen in 27% of patients. Post‐HCT probable IPA was seen in 24% of patients. There were more patients with pre‐HCT chest HRCT findings satisfying EORTC clinical criteria (45% vs. 18%, P =.014) and GMI ≥0.5 (45% vs. 21%, P =.03) in the group with post‐HCT IPA compared to those without IPA. There was higher day+100 mortality in patients with post‐HCT IPA (55% vs. 18%, P =.001). Conclusions: The presence of EORTC clinical criteria on pre‐HCT chest HRCT, serum GMI ≥0.5, and prior history of IPA predicted post‐HCT IPA. [ABSTRACT FROM AUTHOR]

Familial periodic fever (FPF) is an uncommonly diagnosed autosomal dominant disorder caused by a genetic alteration in the TNFRSF1A gene. These patients usually present with fever which is usually under-investigated and under-diagnosed. In untreated cases, amyloidosis is a frequent complication. We present a 24 years male who had a history of fever from childhood, however, remained undiagnosed short of genetic testing. He has recurrent episodes of fever. During the episodes of fever, he was found to have leukocytosis (total leukocyte count- 25.7 x10^9/L) and neutrophilia (absolute neutrophil count- 22.7 x10^9/L) both of which came back to normal limits as the fever subsided. On further evaluation for neutrophilia, the exclusion of common causes of neutrophilia was done. Next-generation sequencing detected a missense variant in TNFRSF1A : c.215G > A (p.Cys72Tyr) which was confirmed by Sanger sequencing. This variant has been described in the literature in anecdotal cases of FPF. This is a first case report from the Indian subcontinent reporting TNFRSF1A : c.215G > A (p.Cys72Tyr) variant in a patient of FPF. Short of genetic testing, the fever would remain a diagnostic dilemma in this patient. This report highlights the importance of targeted resequencing in clinching diagnosis in such patients. [ABSTRACT FROM AUTHOR]

Acute Promyelocytic Leukemia (APL) is associated with excellent long-term outcomes. However, early mortality due to coagulopathy remains a challenge. In this study we examined the bleeding and thrombotic manifestations, as well as incidence of Early Death secondary to thrombosis/hemorrhage (ED-TH) in patients with APL. Early death (ED) was defined as death occurring within 30 days of induction therapy. Two-hundred forty-eight patients were included in the study. Overall, 57 patients had evidence of a major bleed/thrombosis at presentation or during induction therapy, including 44 patients with a major bleed, 8 patients with thrombosis and 5 patients with both evidence of thrombosis and a major bleed. Forty patients (16.1%) had ED, of which 21 had ED-TH. The cumulative incidence of death due to thrombo-hemorrhagic complications at 30 days was 8.4%. On univariate analysis, increasing Prothrombin time (PT)(p-<0.001), white blood cell count (p < 0.001) and activated Partial thromboplastin time (aPTT) (p < 0.001) were statistically significantly associated with increased risk of ED-TH. However, on multivariate analysis, only increasing PT (p-0.025) and aPTT (p-0.041) were significantly associated with increased risk of ED-TH. • Bleeding/Thrombosis is majorly responsible for early death in Acute Promyelocytic Leukemia (APL). • Factors associated with early death due to bleed/thrombosis (ED) in APL patients were analysed. • Prothrombin Time and activated partial thromboplastin time were associated with increased risk of ED. • Better predictors of ED may help improve outcomes further in patients with APL. [ABSTRACT FROM AUTHOR]

Introduction: The quality of life (QoL) analysis is likely to differ by region, ethnicity, and questionnaires in comparison with age‐matched healthy controls. Methods: The EORTC QLQ‐C30 and QLQ‐CLL17 questionnaire validated in regional languages were administered to 127 consecutive CLL and 100 age‐matched, healthy controls at a single center from 2018 to 2019. Results: All groups of CLL patients either on wait and watch (W&W) or on treatment had significantly impaired QoL in all functional domains including global health compared to controls (P <.0001). CLL patients had significantly higher symptom scores than controls in most domains (P <.0001, 0.03 for diarrhea). There was no difference in the QoL by age or gender. Lower socioeconomic status patients had higher financial difficulty (P =.02). Patients on CIT had the worst global health (OR 12.21 compared to patients on W&W) (P =.03). Patients on ibrutinib had less worries/fears about health and functioning than patients who were on CIT (P =.04). Conclusions: Quality of life is severely affected in CLL patients on W&W. Global health status and worries about future health and functioning were major concerns. Socioeconomic status but not age or gender impacted QoL. Patients on ibrutinib had better QoL than on CIT. [ABSTRACT FROM AUTHOR]

Background: Therapeutic whole blood exchange (TWBE) has been used as an alternative when methylene blue (MB) fails in severe methaemoglobinemia. However, there are limited data on the efficacy and safety of TWBE. Objectives: Our aim was to report our institutional experience with TWBE. We also perform a systematic review of published literature. Methods: We retrospectively reviewed our respiratory intensive care unit database to identify cases of methaemoglobinemia managed with TWBE. A systematic review of the PubMed database was performed to identify similar cases (≥12 years). We report the indications, utility, and safety of therapeutic exchange in methaemoglobinemia. The procedural details were also noted. Results: We identified five subjects who received TWBE for methaemoglobinemia (median methaemoglobin level 39%; range 19.6‐42.4%). TWBE was successful in all five cases and no adverse events were encountered. Our review identified 27 additional subjects. The median methaemoglobin level was 37.5% (range 3.7‐81%). The most common indication (n = 24, 75%) for therapeutic exchange was a lack of response to MB. A majority of the subjects (n = 26/32, 81.2%) survived. No procedure‐related complications were reported. Conclusion: TWBE is a safe and effective salvage modality for adults with methaemoglobinemia, when MB is either contraindicated or ineffective. Future studies should standardise therapeutic exchange in the management of methaemoglobinemia. [ABSTRACT FROM AUTHOR]

Summary: Mesenchymal stromal cells (MSCs) demonstrate the properties of self‐renewal, multipotentiality, and immunosuppression, which are responsible for their widespread clinical applications in tissue repair and regeneration. MSCs have been isolated from bone marrow, adipose tissue, and cord blood using culture in specialised media. Their presence in peripheral blood (PB) is debatable. We studied the presence of MSCs at baseline (PB) and following mobilisation with growth factors [PB and apheresis product (AP)] in patients undergoing autologous stem cell transplantation and healthy donors using flow cytometry. We conclude that both mobilised PB and AP are potential sources of MSCs. Given their small numbers in PB/AP, clinical use is feasible following ex‐vivo expansion. Variables affecting the presence of MSCs in PB and AP are also discussed. [ABSTRACT FROM AUTHOR]

Despite the general recommendation to avoid Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML) during pregnancy, unplanned pregnancies still occur, particularly among female patients residing in low- and middle-income countries (LMICs). We aimed to investigate the outcomes of pregnancy, foetal development, and disease progression among female CML patients in chronic phase (CML-CP) undergoing TKI therapy who encountered unplanned pregnancies in a tertiary care hospital in northern India. We conducted a retrospective analysis of all pregnancies in female CML-CP between January 2002 and December 2022 at our hospital. Patients were included if they had a confirmed diagnosis of CML-CP, were receiving TKI therapy during conception, and had available medical records. We analysed the data on pregnancy outcomes, foetal development, and disease progression through a review of medical records. We identified 36 pregnancies in female CML-CP patients on TKI therapy during the study period, with 33 (91.7%) being unplanned. Sixteen pregnancies (48.5%) were conceived at less than major molecular remission (MMR) status. Twelve pregnancies (36.4%) were electively terminated, 4 (12.1%) had miscarriages, and, 17 (51.5%) pregnancies resulted in childbirth. Out of the 17 childbirths, 10 were full-term deliveries, and 7 were preterm deliveries. Twin pregnancies had a high incidence (18.2%). Among the 21 pregnancies that were not electively terminated, TKI was stopped at the first pregnancy detection in 14 pregnancies, while imatinib was continued throughout 7 pregnancies. Patients who discontinued TKI had a higher but statistically non-significant incidence of adverse pregnancy outcomes compared to those who continued imatinib throughout pregnancy (64.2% vs. 28.6%, p = 0.18). Additionally, the risk of long-term disease progression among patients who discontinued TKI during pregnancy and those who continued imatinib throughout pregnancy was 21.4% and 16.7% (p = 0.9), respectively. The risk of long-term disease progression was significantly increased in those persistently at less than MMR pre- and post-gestation (p = 0.0002). Our findings suggest that continuing imatinib therapy during pregnancy, may be a reasonable option for CML patients residing in low- and middle-income countries to reduce the risk of disease progression and adverse pregnancy outcomes. Patients persistently at less than MMR levels pre- and post-gestation should be closely monitored for the risk of long-term disease progression. Further studies with larger sample sizes are needed to confirm these results. • High incidence of unplanned pregnancies noted in female chronic myeloid leukaemia patients on tyrosine kinase inhibitors. • Continuing imatinib during pregnancy may be a reasonable option for CML patients residing in low-and-middle-income countries. • Long-term disease progression is higher in patients with poorly controlled CML who discontinue therapy during pregnancy. • Patients without major molecular remission pre-and post-gestation require close monitoring for long-term disease progression. [ABSTRACT FROM AUTHOR]

The data on adolescent and young adult chronic myeloid leukemia (AYA-CML) from the Indian subcontinent are scarce. We studied characteristics of AYA-CML through a retrospective analysis of 1950 CML patients registered to a tertiary care hospital in Northern India. AYA-CML represented 22.1% of all CML patients, with cumulative overall survival (OS) of 84%, and 1 and 8 years OS of 94.2% and 74.2%, respectively. Of all cases, 8.91% patients had advanced disease at the time of diagnosis, and 13.95% had myelofibrosis in the diagnostic marrow, 79.6% had complete cytogenetic response (CCyR), and 84.5% had major molecular response (MMR). Loss of CCyR and MMR was noted in 37.2% and 28.4%, respectively. The cumulative OS was significantly better in patients on patient assistance program, and they were initiated on therapy within 3 months of symptom onset. [ABSTRACT FROM AUTHOR]

Objectives: Danazol is an attenuated androgen and is used in the treatment of aplastic anemia (AA) in resource constraint settings. We chose to study the role of CD4+ CD25high CD127low FoxP3+ T regulatory cells (T-regs) in the pathophysiology of AA and their response to treatment with Danazol alone or in combination with immunosuppressive treatment (IST). Methods: T-regs' percentages of 25 acquired idiopathic AA patients and 25 healthy controls who completed study protocol were analyzed by performing multicolor flowcytometry on peripheral blood samples. Results: More than one-third (36%) of AA patients in our study received Danazol as monotherapy, whereas less than a third (32%) each received standard doses of IST with equine Anti Thymocyte Globulin (ATG) and Cyclosporine combination, or Cyclosporine and Danazol combination, respectively. Results showed that all AA patients had a significantly lower percentage of T-regs at the time of diagnosis when compared to healthy controls (p < 0.0001), implicating their role in the pathophysiology. On treatment, all 25 patients showed a significant rise in the percentage of T-regs when compared to baseline (p < 0.0001). Discussion: The rise in T-regs' percentage was higher in patients treated with Danazol alone when compared to standard IST (ATG with Cyclosporine), or Cyclosporine with Danazol combinations (p = 0.585). Conclusion: We conclude that Danazol also leads to increase in T-regs in acquired idiopathic AA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Short‐term mucocutaneous adverse effects are well documented with imatinib. However, studies on long‐term adverse effects and in the ethnic population are lacking. Objective: To study the long‐term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. Methods: In this cross‐sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Results: Four hundred and thirty‐eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma‐like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug‐induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Conclusion: Cutaneous hyperpigmentation and periorbital edema are common long‐term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects. [ABSTRACT FROM AUTHOR]

Introduction: Multiple myeloma (MM) is considered as a disease of the old with the reported median age of 60-70 years. The disease occurred a decade earlier in the Indian subcontinent. The literature on MM in adolescents and young adult (AYA) is limited. We studied the disease characteristics and outcomes of the AYA-MM in the real-world setting. Patients and methods: It is a retrospective single-center study conducted at a tertiary care center from North India. Records of all consecutive patients with AYA-MM (15-39 years of age) who were managed from January 1, 2010, to December 30, 2015, were reviewed. Survival was assessed from the date of start of treatment to the last follow-up date or death due to any cause. Results: A total of 415 patients managed for MM were included in the study. The frequency of the AYA-MM was 9.6% (40/415) of whom 5 patients were younger than 30 years. There was male preponderance with a median age of the patients being 38 years. The main presenting features were bone pain (55%), fatigue (45%), extramedullary plasmacytomas (20%), and infections (12%) and referral from the peripheral hospital as renal dysfunction (58%). On the evaluation of patients, hypercalcemia, renal impairment, anemia, and lytic lesions were seen in 24.32%, 30%, 52.5%, and 59.25% of patients, respectively. The majority had the high-risk disease (International Staging System [ISS]-III: 75%). Only 22.5% patients were transplanted. The 3-year median overall survival of the study population was 80.21%. Conclusion: AYA-MM patients have a higher prevalence of extramedullary disease and high-risk disease. [ABSTRACT FROM AUTHOR]

Purpose The introduction of tyrosine kinase inhibitors has transformed the care of patients with chronic myeloid leukemia, with survival approaching that of healthy individuals. Current-day challenges in chronic myeloid leukemia care include adherence to tyrosine kinase inhibitor therapy.Westudied adherence from resource-constrained settings and tried to analyze the factors responsible for nonadherence in these individuals. We also correlated adherence to current molecular status. Patients and Methods This was a single-center, cross-sectional, observational study from north India. It consisted of a questionnaire-based survey in which a one-to-one interview technique was used by trained nursing staff administering the Modified Morisky Adherence Scale (MMAS-9) questionnaire. Adherence was also measured on the basis of physician’s assessment. JMP 13.0.0 was used for statistical analysis. Results A total of 333 patients with a median age of 42 years were included in the study. The median BCRABL/ ABL ratio (IS) was 0.175 (0.0 to 98.0). The mean MMAS-9 score was 1162. Adherence was seen in 54.95% on the basis of MMAS-9, whereas physician’s assessment reported adherence in 90.39% of patients. Using the x2 test, no relationship was found between the two assessment techniques. There was a significant relationship between major molecular response status and adherence by physician’s assessment and MMAS-9 (P < .001). Bivariate analysis by logistic fit showed a good relation between the MMAS-9 score and the BCR-ABL/ABL ratio (IS), x2 (1,220) = 135.45 (P < .001). On multivariate analysis, enrolment in the Novartis Oncology Access program (a patient assistance program) was significantly associated with adherence (P = .012). Conclusion This study highlights the lack of adherence in real-world settings and the various factors responsible. Such studies are important from a public health services perspective in various settings around the world because they may lead to corrective action being taken at the institutional level. [ABSTRACT FROM AUTHOR]

Purpose: The introduction of tyrosine kinase inhibitors has transformed the care of patients with chronic myeloid leukemia, with survival approaching that of healthy individuals. Current-day challenges in chronic myeloid leukemia care include adherence to tyrosine kinase inhibitor therapy. We studied adherence from resource-constrained settings and tried to analyze the factors responsible for nonadherence in these individuals. We also correlated adherence to current molecular status. Patients and Methods: This was a single-center, cross-sectional, observational study from north India. It consisted of a questionnaire-based survey in which a one-to-one interview technique was used by trained nursing staff administering the Modified Morisky Adherence Scale (MMAS-9) questionnaire. Adherence was also measured on the basis of physician's assessment. JMP 13.0.0 was used for statistical analysis. Results: A total of 333 patients with a median age of 42 years were included in the study. The median BCR-ABL/ABL ratio (IS) was 0.175 (0.0 to 98.0). The mean MMAS-9 score was 11 ± 2. Adherence was seen in 54.95% on the basis of MMAS-9, whereas physician's assessment reported adherence in 90.39% of patients. Using the χ2 test, no relationship was found between the two assessment techniques. There was a significant relationship between major molecular response status and adherence by physician's assessment and MMAS-9 (P <.001). Bivariate analysis by logistic fit showed a good relation between the MMAS-9 score and the BCR-ABL/ABL ratio (IS), χ2 (1,220) = 135.45 (P <.001). On multivariate analysis, enrolment in the Novartis Oncology Access program (a patient assistance program) was significantly associated with adherence (P =.012). Conclusion: This study highlights the lack of adherence in real-world settings and the various factors responsible. Such studies are important from a public health services perspective in various settings around the world because they may lead to corrective action being taken at the institutional level. [ABSTRACT FROM AUTHOR]