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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]

Diarrhea is the major cause of discomfort and morbidity of patients undergoing hematopoietic stem cell transplant (HSCT). The cause of diarrhea may be infective or non-infective. This is a prospective single center observational study from North India conducted over a period of approximately 4 years among 105 patients who underwent HSCT (autologous-72, allogeneic-33). The objective of the study was to identify the overall incidence and characteristics of diarrhea in HSCT in the real world, to evaluate any differences among allogeneic or autologous transplants, incidence of C Difficile among diarrheal patients, and antimicrobial usage among these patients. Diarrhea was present in 89 of 105 patients (84.7%). The mean diarrheal duration was of 8.39±4.57 days (range: 1–24 days). There was non statistical difference between the incidence of diarrhea amongst allogeneic and autologous transplants (78.9% Vs 87.5%). Out of 89 patients with diarrhea, 13 were CDTA positive. We could isolate Clostridium difficile in culture in only 7.6% of patients with CDTA positivity. Metronidazole was the antibiotic of choice for diarrhea in our post-transplant settings. Metronidazole was prescribed for a median duration of 8 days (Range: 3–18 days). Seventeen patients received oral vancomycin with a median duration of 8 days (Range: 5–14 days). We conclude by saying that diarrhea was a common post-transplant morbidity. Clostridium difficile is not common in patients with the diarrhea post hematopoietic stem cell transplant. All cases of diarrhea need not be infective particularly in allogeneic settings. [ABSTRACT FROM AUTHOR]

High-risk single nucleotide polymorphisms (SNPs) in nucleotide-binding oligomerization domain-2 (NOD2) gene are associated with high susceptibility for infections and inflammation due to risk of inappropriate cytokine production and NF- κ B activation. We studied the incidence of three high-risk NOD2 gene SNPs (8, 12 and 13) among BM-transplant (BMT) recipients. Sequential patients undergoing BMT over 1-year period were prospectively studied. Patients were tested with MspI/HhaI or NlaIV restriction-endonucleases (Euryx, Gdansk, Poland) for NOD2 gene SNPs 8, 12, and 13, respectively. Regimen-related organ toxicity was graded using the Seattle-Bearman criteria. Forty patients were enrolled, their median age was 38 years (range 3–64), and 52.5% were males. Twenty patients each (50%) underwent autologous and allogeneic BMT. Majority of the patients (n = 38, 95%) developed febrile-neutropenia in the post-transplant period and 4 patients died due to overwhelming sepsis within day +100. Acute graft-versus-host disease (GVHD) [grade I–II (n = 3) and grade III-IV (n = 6)] was observed in 9/20 allogeneic HSCT recipients. None of our 40 patients showed presence of any of the three NOD2 gene SNPs. The 3 commonly observed high risk SNPs (8,12, and 13) of NOD2 genes were not present in study population. It is quite likely that due to geographical and racial variations these polymorphisms are completely absent in North India. NOD2 gene is highly diverse and polymorphic variants can be absolutely different in various populations. Larger studies targeting sequencing of the whole NOD2 gene can convincingly rule out or confirm the role of NOD2 gene variants in Indian population. [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 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]

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. 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]

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]

Purpose of Review: Chronic lymphocytic leukemia was an ignored leukemia in India until a decade back, given its low prevalence and absence of novel drugs to treat it. Healthcare in India is heterogeneous, with variations in population, health systems, and reimbursement options. We have focused on opinions from three hemato-oncologists incorporating an opinion poll from 44 hemato-oncologists across India on the common issues in CLL to give an idea of the practice pan-India., Recent Findings: More CLL patients are being diagnosed in their early stages. There is an attempt to use prognostic and predictive markers in making shared decisions for managing CLL. There is still a role for chemoimmunotherapy (CIT) in India, given limited health insurance coverage. But with the availability of inexpensive generics, the patient preference for non-CIT options like Bruton's tyrosine kinase (BTK) inhibitors is palpable. The CLL scene in India is changing rapidly. With the wide availability of economical generic small molecule inhibitors, monoclonal antibodies, and coverage by social health insurance schemes, India is poised to cater to most CLL patient needs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Chronic lymphocytic leukemia (CLL) is uncommon in India. There are limited studies on CLL from the Indian subcontinent., Methods: This was a prospective study (2011-2017) of consecutively diagnosed patients with CLL at a single center. The diagnosis, prognosis, treatment indication, response criteria, and adverse events were recorded as per International Workshop on Chronic Lymphocytic Leukemia guidelines. Biosimilar rituximab dosing (375 mg/m 2 ) was fixed for all cycles. Time to next treatment (TTNT) was defined as the time from front-line treatment initiation to next treatment or death from any cause. Overall survival (OS) was defined as the time from treatment initiation until death from any cause., Results: A total of 409 patients with CLL were enrolled over the study period. The median follow-up was 32 months (range, 2-135 months). The median age was 61 years, and 31.8% of patients with CLL were ≤ 55 years of age; 43.3% of patients had a cumulative illness rating scale score ≥ 3. Prognostic fluorescence in situ hybridization data were available in 53.3% of patients. Chlorambucil (94/180; 52.2%) and bendamustine + rituximab (BR; 57/180; 31.6%) were the most common regimens used up front. The overall response rates after front-line therapy were 74.4% and 91.2%, respectively. The TTNT was 33 months and not reached, respectively ( P = .001). Grade 3/4 neutropenia and infections were seen in 52.6% and 38.5% of patients receiving BR. The median OS was not reached in both regimens ( P = .25)., Conclusion: Indian patients with CLL are younger in chronological age but have higher morbidity burden. Treatment outcomes with biosimilar fixed-dose BR are comparable to those reported in the literature. Chlorambucil is still a valid option, given the economic burden of the disease and treatment.

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 χ 2 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), χ 2 (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.