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Management of chronic myeloid leukemia (CML) has been transformed by the use of tyrosine kinase inhibitors (TKIs). Presently in India, five TKIs are approved for the management of CML with distinct safety profiles. The selection of TKIs for chronic phase (CP)-CML patients is based on treatment goals, underlying comorbidities, and specific TKI toxicity profiles. Bosutinib is one of five TKIs indicated for the first-line treatment of CP-CML and patients with intolerance or resistance to prior TKI therapy. It possesses a distinct safety profile among other TKIs, with less cardiovascular adverse events (AEs), albeit the liver-related and gastrointestinal AEs have higher occurrence. The safety and efficacy of bosutinib have been examined in clinical trials; however, there is a paucity of data from Asia. A virtual expert panel meeting was convened to gather expert opinion from India on the selection of bosutinib as a treatment choice for patients with CP-CML. This is a white paper document drafted with the help of an expert panel of 14 oncologists and hematooncologists from India on bosutinib use in CP-CML. The experts concurred that bosutinib has proven efficacy for CP-CML in global randomized clinical trials and is well suited for CP-CML patients with existing cardiovascular comorbidities. However, it was not recommended for patients with gastrointestinal, pancreatic, or renal abnormalities. This review aims to put forth expert opinion and guidance document on key considerations for CP-CML clinical decision-making in India. [ABSTRACT FROM AUTHOR]

Background and Objectives: Extra-intestinal salmonellosis is associated with higher case fatality and is underestimated in the developing countries like India. Here we present a case series of bacteriologically proven extra-intestinal salmonellosis managed at our institute over the past two years. Materials and Methods: Retrospective analysis of bacteriologically proven extra-intestinal salmonellosis over two years between January 2020 to December 2021 was carried out. Medical records were reviewed for site of infection, evidence of any underlying or predisposing illnesses and antimicrobial susceptibility report. Results: Eight patients were diagnosed with extra-intestinal salmonellosis. Male to female ratio was 3:1. Mean age was 44 years. Four were typhoidal and four were nontyphoidal Salmonellae. The extra-intestinal sites involved were purulent aspirates from scrotum, caecum, perianal region, intraperitoneal collection, synovium, and urine. Predisposing factors include chronic myeloid leukemia, HIV and gastric malignancy. All deep seated abscess required surgical intervention. All typhoidal Salmonella (n=4) were sensitive to cotrimoxazole, ampicillin, ceftriaxone. Among nontyphoidal Salmonella, one was resistant to cotrimoxazole; two were resistant to ampicillin, ceftriaxone and three resistant to ciprofloxacin. Conclusion: The diagnosis of extra-intestinal salmonellosis requires a high degree of clinical suspicion and should be included in the differential diagnosis in patients with deep-seated abscesses. [ABSTRACT FROM AUTHOR]

A scientometric study examines the publication's quantitative and qualitative trends in a particular research area. The present study investigates 2,854 leukemia research outputs of India published from 1989 to 2020, indexed in the Web of Science Core Collection database. Software, including bibliometrix Biblioshiny, BibExcel, HistCite and VOSviewer, have been used for data analysis. The Pediatric Blood & Cancer journal has the highest number of published articles. The USA collaborated with the highest number of publications with India. The All India Institute of Medical Sciences had the maximum number of publications. Bakshi S, Sharma A and Varma N were the leading authors of publications about leukemia research in India. Keyword analysis revealed that acute lymphoblastic leukemia, chronic myeloid leukemia, leukemia, acute myeloid leukemia and apoptosis were the main research hotspots in the area in all publications. The Department of Biotechnology (DBT), India and the National Institute of Health (NIH), USA, were the major funders in the leukemia research publications in India. The limitation of the study is that the data used is entirely dependent on the Web of Science (WoS) Core Collection database. So, the quality of the study is entirely dependent on the input information imported from the WoS database. [ABSTRACT FROM AUTHOR]

Donor lymphocyte infusions (DLIs) are often recommended products after allogeneic hematopoietic stem cell transplant to increase graft - versus - leukemia effect. More success rate of DLI has been reported in relapsed posttransplant chronic myeloid leukemia. Whatever the indication for DLI, mortality related to post-DLI infusion is 5%-20%, and more than one-third of patients will develop acute and/or chronic graft versus host disease (GVHD) after DLI. We report two cases where DLIs were used for residual disease after posttransplant. Both of DLI went uneventful. None of the patient's developed signs of GVHD postinfusion. Although both patients expired with different causes, none were related to DLI infusion. Information from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with aggressive diseases may benefit from disease reduction before DLI. However, further evidence is required to evaluate its efficacy, especially in relapsed or residual hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: Juvenile myelomonocytic leukemia (JMML), previously known as juvenile chronic myeloid leukaemia, is a rare, unique, and aggressive myeloproliferative neoplasm of early childhood. Making a diagnosis of JMML is challenging because of the overlapping clinical and haematological features with other myeloproliferative neoplasms (MPN). However, some unique features like monocytosis, the absence of BCR-ABL translocation, and the presence of specific mutations (PTPN-11, K-RAS, N-RAS, CBL, or NF1) clinch the correct diagnosis. Methods: A prospective analysis of six JMML patients with variable clinical features treated with injection azacytidine as frontline therapy during the study period of 2 years. Results: The median age was 4.5 years with male:female ratio 2:4. Pallor and splenomegaly were the most common presenting signs. Four patients (66.67%) achieved complete remission (CR), two patients (33.33%) had partial remission (PR), and one patient (16.67%) had progressive disease (PD). The overall survival rate was 66.67% (four out of six), and the mortality rate was 33.33%. Conclusion: Azacitidine is an effective treatment option as upfront therapy for JMML, especially in resource poor developing countries. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we investigate renal function and anaemia during imatinib treatment in patients with chronic myeloid leukaemia. Methods: The patients with chronic myeloid leukaemia with chronic phase who had been treated with only imatinib for 12 months at Rajiv Gandhi Cancer Institute and Research Centre (New Delhi, India) were enrolled and prospectively analysed. The chronic renal impairment parameters, including estimated glomerular filtration rate and haemoglobin levels for anaemia from June 2020 to June 2022, were monitored in newly diagnosed in patients with chronic myeloid leukaemia-chronic phase. The data were analysed by SPSS software version 22. Results: In total 55 patients with chronic myeloid leukaemia chronic phase who had been on imatinib for 12 months were monitored. The mean estimated glomerular filtration rate was significantly decreased (74 ± 14 to 59 ± 12 mL/min/1.73m2, p < 0.001) with a decrease in mean haemoglobin levels after 12 months (10.9 ± 2.01 to 9.0 ± 1.02, p < 0.004). The decreased estimated glomerular filtration rate was negatively correlated with haemoglobin levels after 1 year of imatinib administration (correlation coefficient = 0.892, R2 = 0.7976, p < 0.05). Conclusion: We recommended close monitoring of renal function and haemoglobin levels in patients with chronic myeloid leukaemia patients. [ABSTRACT FROM AUTHOR]

Background: Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disorder, caused by a balanced reciprocal translocation (t(9;22) (q34;q11)) that leads to the formation of BCR (Breakpoint Cluster Region)-ABL (Abelson) fusion transcripts known as Philadelphia (Ph) chromosome. The prevalence of BCR-ABL fusion transcripts in Indian CML population is poorly understood, and few studies have been reported from India. The aim of the present study was to determine the frequencies as well as prognostic effects of the three fusion transcripts, i.e. b2a2, b3a2 and e1a2 in an Indian population. Methods: RNA was isolated from total 123 samples, 27 bone marrow (BM) samples and 96 peripheral blood (PB) samples, of CML patient followed by cDNA synthesis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed using TaqMan® assay (ABI, CA, USA) to monitor BCR-ABL transcript. Results: Ph' chromosome was observed in 103 patients whereas it was not detected in 20 cases. qRT-PCR revealed that the b3a2 fusion transcripts were the most common transcript in CML patients (63.41%) while b2a2 fusion transcript was present in 16.26% cases. Co-expression of b3a2 + b2a2 fusion transcript was observed in 0.81% cases whereas co-expression of b3a2 + e1a2 fusion transcript was found in 1.63% cases. There was no correlation observed between b3a2 fusion transcript and platelet count. The fusion transcript b2a2 was observed in relatively younger patients compared to b3a2 fusion transcript. Although this correlation was not statistically significant. Conclusion: The co-expression of BCR-ABL fusion transcripts was higher (63.41% aggregate of b3a2) in the present population in contrast with other populations reported. This finding was consistent with the frequency data reported from Sudan. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In India, there is a high burden of infections such as tuberculosis, dengue, and malaria which are common causes of monocytosis. This increases the workload of smear examination by the pathologist. "Mono-dysplasia score" is obtained with a simple complete blood count on an automated cell counter and includes the parameters neutrophil (Ne) and monocyte (Mo) count and Ne-WX which is a Ne dispersion parameter. It is operator independent, objective, and does not require a high level of expertise. AIMS: The aims of the study were to assess the utility of Monoscore/mono-dysplasia score calculated using research parameters of Sysmex XN automated cell counter, as a screening tool for differentiating reactive monocytosis from hematological malignancies associated with monocytosis. MATERIALS AND METHODS: Samples sent in EDTA vacutainer for routine hemogram fulling the criteria for monocytosis (WHO criteria - absolute monocyte count =1 × 109/L and accounting for =10% of the total white blood cell count) were included in the study. Monoscore was calculated using the formula established by Schillinger et al. Flow cytometry, bone marrow examination, etc., were done as and when needed as standard-of-care tests to establish a final diagnosis. RESULTS: One thousand two hundred and fifty-seven samples were analyzed out of which 41 samples were chronic myelomonocytic leukemia and 126 were other hematological malignancies (HD) including acute leukemias, myelodysplastic syndrome, myeloproliferative neoplasm, etc. Using receiver operating characteristics curves, we established the cutoff 0.212 which showed a sensitivity of 97.6% and specificity of 96.4% to differentiated reactive monocytosis form HD. CONCLUSIONS: A sample showing monocytosis and Monoscore <0.212 and without any other flags can be safely auto-authorized without peripheral blood smears examination, reducing the burden of slides to be reviewed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Imatinib mesylate is the cornerstone therapy in the management of chronic myeloid leukemia (CML). Monitoring of adverse drug reactions (ADRs) of imatinib in our patients is very important to ensure their safety. Aims and Objectives: The current study aims to monitor ADRs encountered in CML patients in the chronic phase with imatinib (400 mg/day). MATERIALS AND METHODS: This prospective, observational study was conducted from November 2011 to May 2015 on 310 patients presented to the Departments of Clinical Hematology and Pharmacology of SCB MCH, Cuttack, diagnosed with CML at chronic phase. Collected ADRs were entered in the ADR reporting form (PvPI) and were analyzed for causality and severity. RESULTS: Anemia was the most common hematological ADR, whereas hyperpigmentation and nausea were the most common nonhematological ADRs reported. Maximum ADRs were mild to moderate and required no change in the treatment course. CONCLUSION: The study revealed that imatinib mesylate, a well tolerated drug, has very few cases of severe ADRs in Indian patients at the chronic stable phase of CML. [ABSTRACT FROM AUTHOR]

Aims and Objectives: Haematological malignancy may show varied presentation in different regions of world, however, Uttarakhand lacks any recent data about them. The present study was therefore conducted to study the pattern of haematological malignancies on bone marrow examination in institute of Uttarakhand. Materials and Methods: This study was conducted at All India Institute of Medical Sciences, Rishikesh, Uttarakhand, over a period of 3 years. It included patients of haematological malignancies diagnosed on bone marrow examination. Patient's age, sex, clinical history and bone marrow diagnosis were noted for every case. All the data were entered into the excel sheet and statistically analysed. Results: The study included total 256 cases of haematological malignancies with male:female ratio of 1.13:1 and mean age of 39.3 years. Chronic myeloproliferative neoplasm (CMPN) was the most common haematological malignancy (49%) with chronic myeloid leukaemia (CML) being its most common type (40%). All the haematological malignancies showed male preponderance except for non-Hodgkin's lymphoma. Mean age of CMPN was 45.81 years and of acute myeloid leukaemia was 36.92 years. Bone marrow aspirate (BMA) and trephine biopsy (BMT) together were able to diagnose 81.3% of cases of haematological malignancies. Conclusion: The study concludes that haematological malignancies present at lesser age with male preponderance in Uttarakhand. CML is the most common haematological malignancy followed by acute lymphoblastic leukaemia. BMA and BMT are complimentary to each other for diagnosis of haematological malignancies and should be used together to avoid missing of any case. [ABSTRACT FROM AUTHOR]

Introduction: Glutathione S‐transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML). We aimed to analyze relation of different GST gene sequence variants with susceptibility and response to Imatinib in CML. Material and Methods: A total of 150 CML cases and equal number of age and gender matched healthy controls were genotyped for five GST polymorphisms by multiplex‐PCR and PCR‐RFLP techniques. BCR‐ABL1 transcripts were quantified by quantitative Real Time PCR (qRT‐PCR). Results: GSTT1, GSTO1, and GSTO2 SNPs revealed no association, while as GSTM1null genotype was observed to protect against the development of CML (OR = 0.53, P =.01). GSTP1 variant genotypes AG (OR = 2.1, P =.003) and GG (OR = 5.6, P <.001), significantly associated with increased risk of CML. Combined genotype analysis showed protective impact of GSTT1present/GSTM1null (OR = 0.44, P =.003) while as GSTT1present/GSTP1‐GG (OR = 6.92, P <.001) and GSTM1present/GSTP1‐GG (OR = 6.33, P <.001), significantly increased CML risk. GSTM1null genotype individually and in combination with GSTT1present associated with superior rate of major molecular response (MMR) and event free survival (EFS) (log‐rank P =.029). GSTO2‐AG+GG genotype associated with significantly inferior MMR rates at 3, 6, and 12 months. Also, patients with GSTO2‐GG genotype showed significantly reduced EFS (log‐rank P =.025). Multivariate analysis confirmed GSTM1null as a better (HR:0.19, P =.029) and GSTO2‐GG genotype as an independent poor prognostic factor (HR:2.29, P =.037). Conclusion: GSTM1null genotype seems to have a better prognostic role while GSTP1 variants significantly increase CML risk. Also, results support a correlation between disease outcome and GSTO2 polymorphism. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukaemia is a clonal disorder arising from hematopoietic stem cell, affecting all the lineage of haematopoietic stem cells. The average age of affection in chronic myeloid leukemia is 60 to 65 years and is extremely rare in childhood comprising 3% of paediatric leukaemia. An institution-based study was carried out to reveal the statistics of pediatric chronic myeloid leukaemia patients in a tertiary health care centre of North India serving mainly the economically under privileged population belonging to minority groups. [ABSTRACT FROM AUTHOR]

Introduction: Outcomes in chronic myeloid leukemia (CML) have vastly improved after introducing tyrosine kinase inhibitors. However, patients in low and middle-income countries (LMICs) face many challenges due to social and financial barriers. Objective: This study was conducted to understand socio-economic hindrances, knowledgeattitudes-practices, and assessing nonadherence to treatment in chronic phase CML patients taking imatinib. Materials and Methods: Patients of chronic phase CML, aged 15 and above, taking imatinib for six months or more were included in the study. A questionnaire (in the Hindi language) was administered, inquiring about the nature of the disease and its treatment, how imatinib was obtained, drug-taking behavior, and the treatment's economic and social burden. Nonadherence was assessed by enquiring patients for missed doses since the last hospital visit and for any treatment interruptions of =7 days during the entire course of treatment (TIs). Results: Four hundred patients were enrolled (median age 37 years, median duration on imatinib 63 months). Patients hailed from 16 different Indian states, and 29.75% had to travel more than 500 kilometers for their hospital visit. Scheduled hospital visits were missed by 14.75%. A third of the patients were unaware of the lifelong treatment duration, and 41.75% were unaware of the risks of discontinuing treatment. Treatment was financed by three different means-61.75% received imatinib via the Glivec International Patient Assistance Program (GIPAP), 14.25% through a cost-reimbursement program, and 24% self-paying. 52.75% of patients felt financially burdened due to the cost of drugs (self-paying patients), cost of investigations, the expenditure of the commute and stay for the hospital visit, and loss of working days due to hospital visits. 41.25% of patients reported missed doses in the last three months, and 9% reported missing >10% doses. 16.5% of patients reported TIs. Nonadherence>10% and TIs were significantly higher in selfpaying patients (15.6% and 25% respectively). Conclusion: We observed that patient awareness about the disease was suboptimal. Patients felt inconvenienced and financially burdened by the treatment. Nonadherence and treatment interruptions were observed in 41.25% and 16.5%, respectively. These issues were prevalent in self-paying patients. [ABSTRACT FROM AUTHOR]

In India, CML is the commonest adult leukemia. Imatinib is the gold standard for frontline treatment of newly diagnosed CML-CP patients. The present study was conducted to assess the efficacy and safety of generic imatinib in newly diagnosed CML-CP patients. In this prospective study, 76 newly diagnosed CML-CP patients received generic imatinib. They were monitored as per the ELN2013 recommendation. Karyotyping and BCR-ABL transcript level were done at specified time points. Adverse effects, if any, were documented as per the NCI-CTCAE criteria v4.03. Statistical analysis was done using standard methods. A total of 76 patients included in the study; median age was 36 years. The most common (71%) presenting symptom was fatigue; splenomegaly was found in all patients. CHR was achieved in 97% cases. At 3 months, 64.5% patients achieved ERM. At 6 months, CCyR and MCyR had seen in 65% and 68% cases, respectively. MMR achieved at 12 months in 44% cases. Most common hematological and non-hematological toxicity were anemia and skin changes seen in 89.5% and 71% cases, respectively. With generic imatinib therapy, the results of treatment outcome and safety profile were comparable with original imatinib. The added advantage was gross reduction in cost of therapy meeting unmet needs in CML patients in countries with resource constraints. [ABSTRACT FROM AUTHOR]

A combination of haematological parameters with morphological evaluation of peripheral blood and bone marrow blast cells is crucial for leukaemia diagnosis. FAB (French- American-British) classification is a simple and powerful diagnostic tool for leukaemia in developing countries like India. Differentiation block in the early stages of haematopoiesis and morphological characteristics of leukemic blast cells are directly related to haematological parameters. The present study is an approach to increase understanding of the simple morphological FAB classification of leukaemia in relation to haematological parameters. The present study revealed that Chronic Myeloid Leukaemia (CML) was the most common type of leukaemia, followed by Acute Myeloid Leukaemia, Acute Lymphoid Leukaemia (ALL), and Chronic Lymphoid Leukaemia (CLL) in Nagpur. Most of the cases of Acute Leukaemia had severe anaemia and thrombocytopenia. Highest variation was found in Total WBCs count of different types of leukaemia, particularly in different subtypes of AML. The present study also suggested that FAB classification is not outdated, but it does require continuous revalidation and other procedures for refinement. [ABSTRACT FROM AUTHOR]

PURPOSE: Chronic myeloid leukemia (CML) is the commonest hematologic malignancy in India. There are not many systematic Indian studies that assess response to generic Imatinib mesylate therapy on a large scale, since most published trials from the West and India are with Gleevec (Novartis). METHODS: 101 patients of Chronic Myeloid Leukemia in chronic phase (CML-CP) with a minimum follow up period of 2 years, who had presented to a tertiary care hospital in Western India between 2007 and Feb 2017, were included in this study. All patients received treatment with generic Imatinib Mesylate therapy. Clinical and laboratory examination done at baseline and on follow-up at 1,3,6,9,12 and 24 months was noted. Molecular monitoring with RQPCR at 3 months, 6 months, 12 months and 24 months for BCR: ABL was done. RESULTS: The study was carried out in 101 CML patients (78 males and 23 females) with a median age of 38 years (4 - 77) years at the time of diagnosis. Complete hematological response was noted in 63 (62.4%) at 1 month, 94 (93.1 %) at 3 months, 95 (94.1 %) at 6 months, 97 (96%) at 9 months and 99 (98%) at 12 months. At 12 months, 56 (55.4%) patients achieved Major molecular response (MMR) which was defined as BCRABL: ABL gene levels < 0.1 %. At 24 months, 66 (65.34%) patients were in MMR. CONCLUSIONS: Our study using the Indian generic molecule of Imatinib Mesylate demonstrated comparable hematological and molecular responses as published for the parent molecule, Gleevec (Novartis). [ABSTRACT FROM AUTHOR]

Background: Interleukin 6 (IL6) has been suggested to be a valuable prognostic marker in chronic myeloid leukemia (CML). IL6 is a pleiotropic cytokine and plays an important role in immune response, hematopoiesis, and acute phase response. IL6 is regarded as a prominent target for clinical interventions.Objective: The aim of the present study was to investigate the serum levels of IL6 in CML to provide greater insight to their role in disease transformation in Indian patients.Materials and Methods: A total of 50 CML cases and 10 acute lymphocytic leukemia (ALL) cases along with 20 healthy controls were included in the study between 2015 and 2016. About 4 mL blood samples were collected from all cases in plain vial and serum was separated. Levels of IL6 were determined in all cases by enzyme-linked immunosorbent assay.Results: The study suggests that both ALL and CML are associated with significantly elevated serum IL6 level than the healthy control group. Mean levels of serum IL6 are 223.4 ± 53.403 pg/mL in CML, 71.020 ± 29.549 pg/mL in ALL, and 5.360 ± 0.467 pg/mL in healthy control group. Serum IL6 correlated with different phases of CML. Mean IL6 levels are 50.93 ± 29.37 pg/mL in chronic phase (CP), 69.02 ± 22.60 pg/mL in accelerated phase (AP), and 652.77 ± 124.62 pg/mL in blast crisis (BC) phase of CML. In compared to CP and AP, in BC, IL-6 is significantly elevated ( P = 0.00 and 0.00, respectively); however, we did not find a significant difference in IL-6 serum levels between CP and AP ( P = 0.703).Conclusion: Study suggests that the detection of IL6 level in newly diagnosed patient can predict the severity of the disease. There might be association of level of IL6 with the disease transformation. [ABSTRACT FROM AUTHOR]

Background: The rationale of this study is to reveal the statistics of pediatric chronic myeloid leukemia (CML) patients.Subjects and Methods: It is a retrospective analysis conducted to assess pediatric CML data from January 1998 to December 2014. There are 65 (3.2%) pediatric CML patients out of entire 2008 patients of CML. Data were analyzed regarding epidemiological characteristics, clinical presentations, response and side effects of imatinib, event-free survival, and overall survival of the pediatric CML patients.Results: The median age of diagnosis was 11.84 years, and 76.9% patients were male and 23.07% patients were female. Sixty (92.3%) patients were in CML-chronic phase, 3 (4.6%) patients in CML-accelerated phase, and 2 (3.07%) patients in CML-blastic crisis. Most common initial symptoms and signs are weakness (60.0%), abdominal pain (55.38%), splenomegaly (100%), and hepatomegaly (86.5%). 67.3% of patients have white blood counts <100 × 109/L and 92.3% had platelets >150 × 109/L. In the initial months of 2002, imatinib was available and utilized in 54 patients. Of 54 patients, complete hematological response at 3 months, partial cytogenetic response at 6 months, complete cytogenetic response at 12 months, and major molecular response (MMR) at 18 months were 77.77%, 59.2%, 48.14%, and 40.74%, respectively. MMR at 36 months was 62.96% ( n = 34). Most common imatinib-related side effects are gastrointestinal upset and myelosuppression.Conclusion: Pediatric CML in India is comparable with Western countries regarding epidemiological characteristic, clinical presentations, and tolerance of imatinib. As there is a paucity of universal literature regarding pediatric CML (especially data from Southeast Asian region), this article may fill up that space. [ABSTRACT FROM AUTHOR]

The use of imatinib has brought a standard shift in the management of chronic myeloid leukemia (CML) during the last two decades. In India, imatinib has been available for more than fifteen years and has been made available all over the country due to patient assistance programs and cheaper generic versions. Despite improvements in survival of CML patients, there are unique challenges in the Indian context. Indian patients present with more advanced disease. Most centers have access to imatinib as first-line therapy, but there is limited availability of molecular monitoring and second-line therapy. Most of the outcome data is retrospective and comparable with that reported in Western centers. Drug adherence is impaired in at least one third of patients and contributes to poor survival. The aim of this review is to highlight the fact that prospective studies and cooperative studies are very much needed to improve the quality of data available on Indian CML patients. [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]

Objective: Data on outcome of patients with ischemic priapism (IP) due to malignant causes are scant. In this study, we compared outcome of patients with malignant vs. non-malignant IP in adult North Indian men. Material and methods: We analyzed medical records of patients with IP who presented to a large tertiary care referral center from August 2005 to July 2017. Results: Data of 71 patients were analyzed. The median age was 30 years (range 17-65). The average duration of symptoms was 4.39 days (range 1-10). Most common etiology was idiopathic in 29 (40.84%), chronic myeloid leukemia (CML) in 24 (33.80%), and drug-induced in 15 patients. Thirty-eight patients underwent distal shunts, while nine patients underwent proximal shunt procedure. Men with malignant priapism (CML) had significantly lower success rates with interventions, prolonged hospital stay, and higher complications (p<0.05). Most complications after shunt surgery were minor (Clavein grade 1 and 2). After shunt surgery, bleeding at shunt site was observed in 14 cases, and wound infection developed in five patients. Prevalence of erectile dysfunction in patients at follow-up was high. Conclusion: Men with malignant priapism (CML) had significantly lower success rates with interventions, prolonged hospital stay, and higher complications than men with non-malignant priapism. [ABSTRACT FROM AUTHOR]

Background: Methylenetetrahydrofolate reductase (MTHFR) gene is a crucial regulator of folate metabolism and its two prominent polymorphic variants C677T and A1298C lead to decreased MTHFR enzyme activity. Aim of the Study: We planned this case–control study based on numerous studies supporting the association of MTHFR polymorphisms (C677T and A1298C) with CML risk in different ethnic populations. Therefore, the influence of these polymorphisms on CML susceptibility was investigated among Kashmiri population (North India). Materials and Methods: Polymerase chain reaction/restriction fragment length polymorphism (RFLP) technique was employed for genotyping MTHFR C677T and A1298C SNP's in 125 CML patients as against 150 age and gender matched healthy controls. Results: A significant difference was observed in frequency of 677CT genotype between cases and controls [46.4 vs. 27.3% (p = 0.0005)]. Similarly combined 677CT+TT genotype showed significant difference between cases and controls [50.4 vs. 28.6% (p = 0.0002)]. Both MTHFR 677CT and 677CT+TT genotypes imposed greater than 2-fold risk of developing CML (OR = 2.4, 95%CI: 1.46–4.05; OR = 2.5, 95%CI: 1.53–4.16). In case of A1298C SNP, the frequency of 1298AC genotype was higher in controls (64.0%) as compared to CML cases (48.8%) (p = 0.04) and imparted a significant protective role from CML predisposition. Furthermore, haplotype analysis revealed only "677CT/1298AA" haplotype significantly increased the risk of CML predisposition [(p = 0.008) (OR = 3.2, 95% CI: 1.3–7.4)]. Conclusion: We conclude that both MTHFR C677T and A1298C polymorphisms may be important genetic modifiers and seem to have a plausible role to confer risk of CML in Kashmiri population, where C677T SNP strongly increases the risk of CML while as A1298C SNP has a protective effect. [ABSTRACT FROM AUTHOR]

Introduction: Chronic myeloid leukemia (CML), a chronic hematologic malignancy, is rare in pediatric patients. Studies of the tyrosine kinase inhibitor imatinib are required so that uniform guidelines may focus on disease therapy and follow-up for children. We analyzed the clinicohematologic features of the disease, treatment response to imatinib, follow-up measures, and the impact of the disease on the patients and their family. Materials and Methods: All pediatric patients diagnosed with CML and treated and followed-up were studied regarding demographics, clinical features at presentation, and diagnostic profile, including laboratory parameters, peripheral blood smear test, fluorescent in situ hybridization and karyotyping, and reverse-transcriptase polymerase chain reaction for the BCR-ABL fusion gene. Treatment modalities, adverse reactions, remedial measures, assessment at every follow-up visit, patient's education, parents' socioeconomic status, and economic and psychological stresses were also evaluated. Results: Six patients were administered upfront therapy with a standard dose of imatinib. Hematological and biochemical parameters were monitored after the drug administration. We assessed the treatment response using molecular detection of the BCR-ABL transcripts. All patients who complied with drug therapy showed a complete molecular response and minimal toxic symptoms. However, parents found it difficult to cope socially and economically. Conclusion: Imatinib mesylate is effective and has a good molecular response, minimal toxicity, and good patient compliance. However, due to its cost, families reacquire financial debt, and the disease creates uncertainty about the child's future, thereby necessitating psychosocioeconomic support for parents. Changes in the policies of cancer support groups are urgently needed to provide lifelong, lifesaving drugs free of cost. [ABSTRACT FROM AUTHOR]

Context: Chronic myeloid leukemia (CML) is one of the most common hematological malignancies in all populations throughout the world. Even though the pathophysiology of CML was well explained in majority of the studies, the incidence of CML was shown to exhibit population diversity, and hence, the demographic factors underlying CML origin remain to be understood. Further, the introduction of tyrosine kinase inhibitors had revolutionized the treatment of CML over the years; however, there is a need for developing tailoring therapy to individual risk since the patient clinical heterogeneity poses a major problem during drug response. Therefore, the study of basic clinical picture may aid in planning treatment strategies for CML patients. Aim: The aim of this article is to study the epidemiological and clinical variables associated with the prognosis of CML. Subjects and Methods: We have considered the distribution of various demographic and clinical variables among 476 CML patients diagnosed at Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India. Statistical Analysis Used: All the analyses were performed through SPSS software (version 21.0). Correlation and Cox regression analyses were also performed. Results: Apart from the elevated male sex ratio in CML incidence, high frequency of males was observed to be nonresponders to imatinib mesylate (IM). IM response was shown to be dependent on phase of diagnosis, whereas overall survival of CML patients depends on the age at onset and response to IM. Conclusions: The study of epidemiology and clinical picture of CML patients may help in planning better treatment strategies at diagnosis to achieve long-term progression-free survival. [ABSTRACT FROM AUTHOR]

Introduction: Myeloproliferative disorders are characterized by proliferation of one or more myeloid lineages cells. In order to assess the burden of these illness for public health planning, it is important to know their frequency. Objectives: A study to determine the clinical, hematological, cytogenetic, and molecular profile in chronic myeloid leukemia (CML) patient in and around Eastern UP, India. Materials and Methods: Newly diagnosed and follow-up adult and pediatric cases of myeloproliferative disorder were taken into study. Detailed history, physical, and systemic examination was done with informed consent. Investigations like complete blood count including hemoglobin level, platelet count, total and differential leucocyte count, general blood picture, and bone marrow aspiration/biopsy were done. Molecular and cytogenetic studies were also done whenever required. Results: In total, 90 patients were enrolled in the study. The median age of presentation of CML was 37 years and the mean age was 38.6 years. M: F ratio of 1.4:1.75 patients (83%) were in CML-chronic phase (CP), 11 patients (12%) in CML-accelerated phase (AP) phase, and 4 patients (5%) were found in CML-blast crisis (BC) phase. The common symptoms of the patients were fullness of the abdomen (66.6%). Among these 69 cases, Philadelphia chromosome was present in 65 (94.2%) cases. Revers transcriptase polymerase chain reaction (RT–PCR) was done in 40 out of 90 cases, breakpoint cluster region (BCR)-Abelson oncogene (ABL) gene came out to be positive in all the 40 cases. Conclusion: Most CML patients in eastern UP (India) are relatively young (31–40 years). In addition, males were more commonly affected. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is a myeloproliferative disorder with clonal expansion of transformed primitive hematopoietic progenitor cells without loss of their capacity to differentiate. Annual incidence of CML in females ranges from 0.6 to 1.6 per 100,000 populations. In developing countries like India where onset of hematological malignancy occurs in early age, thereby increases chances of concomitant occurrence of CML and pregnancy together. Although the incidence is rare, anesthesia management of pregnant female presenting more so for an emergency cesarean section (C/S) is challenging because of the physiological changes during pregnancy, presence of anemia, coagulopathy, immunosuppressant drugs, leukocytosis, and rarely blast cells in circulation. We report the successful management of a 19-year-old primigravida, recently diagnosed with CML, planned for emergency C/S under general anesthesia in view of meconium-stained liquor with fetal distress. [ABSTRACT FROM AUTHOR]

Imatinib is a preferred drug for pediatric Chronic Myeloid Leukemia (CML). Long-term use has inhibitory effects on other tyrosine kinase pathways causing off-target complications such as growth impairment. Our aim was to evaluate impact of long-term use on longitudinal growth in children with CML in Kerala. We hypothesized that the impact would be lesser compared to Northern India as Kerala has the lowest rates of underweight and stunting, with a high literacy rate and per capita income. Children ≤14 years of age, diagnosed with CML and received imatinib for at least 1 year were included. Girls >9 years of age and boys >11 years were considered pubertal. Height Z scores were derived using WHO AnthroPlus. Paired t test compared difference of Z scores in prepubertal and postpubertal age groups. Height Z scores were compared with mid-parental height and sibling height Z scores. Thirty-six children were included (M = 21; F = 15). Median duration of imatinib exposure was 84 months. Decrease in longitudinal growth affected children in both prepubertal and postpubertal age groups. Decrease in height Z scores was more in prepubertal age group when imatinib therapy was initiated (p =.0018). Of 10 patients currently above 19 years (of whom 8 were in pubertal age and 2 in prepubertal age at start of imatinib) none are stunted. Patient's height Z scores was lesser compared to sibling height Z scores (p =.027). Children on continuous imatinib showed a significant stunting when treatment was initiated during prepubertal age. There is a catch-up of growth as the final height reached is within normal limits of WHO reference values. [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]

Background: Non chronic myelogenous leukemia (non-CML)/BCR-ABL-negative myeloproliferative neoplasms (MPNs) include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) (apart from chronic neutrophilic leukemia and chronic eosinophilic leukemia, which are rare). They are uncommon clonal disorders of adults, with an incidence ranging from 0.5 to 3/100,000 persons, BCR-ABL negative, and characterized by the activation of Janus-associated kinase 2 (JAK2). Very few studies have been reported from India. Aims and Objectives: The aims and objectives of this study were to analyze the clinicopathological spectrum and to determine the frequency of JAK2 mutation in patients of non-CML/BCR-ABL negative MPNs. Materials and Methods: Clinical and morphological features and frequency of JAK2 mutation in patients with PV, ET, and PMF were studied at a tertiary care hospital. The material was retrieved from the hematopathology records and reviewed. Results: JAK2V617F mutation was found in 10 of 14 cases (71%) of MPNs, 100% in PV, 50% in ET, and 71% of idiopathic myelofibrosis. The presence of JAK2V617F mutation was associated with a higher hemoglobin level (P < 0.05), a higher TLC (P < 0.05), and higher age (P < 0.05). Results showed that there are morphologic differences, and megakaryocytic morphology represents a useful clue for the differential diagnosis of these three BCR-ABL-negative MPN subtypes. Conclusion: The JAK2 V617F mutation was detected in 71% of patients with MPN disorders. Peripheral blood mutation screening for JAK2 V617F should be incorporated into the initial evaluation of patients suspected to have MPNs. Differences in megakaryocytic morphology provide the histomorphological hallmark of BCR-ABL-negative MPN subtypes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the clinical, biological, and molecular characteristics at diagnosis in children and adolescents with chronic myelogenous leukemia (CML) in the Indian scenario at our tertiary patient care center. Subjects and Methods: We evaluated 51 children and adolescents with CML registered at our clinic, from January 2007 to December 2015. The mean and median of various parameters were calculated using a Microsoft excel sheet and SPSS software version 16. Results: The median age of presentation in children was 16 years; 92.2% of them were older than 10 years, with a higher prevalence in boys than girls (gender ratio 2.6:1). The symptoms at presentation were fatigue, fever, awareness of mass due to splenomegaly, and bleeding manifestations. One patient presented with Bell's palsy. Markedly raised leukocyte counts were present in 29.4% patients (median white blood cell count >400 × 109 /L). Most of the patients presented in the chronic phase of the disease, four each were in accelerated phase and blast crisis, respectively. Majority of patients were categorized as intermediate risk as per Sokal and Hansford score. About 60.7% of these pediatric patients fell in low-risk category as per European Treatment and Outcome Study score at baseline. A predominance of transcript P210-b3a2 (68%) was observed in the children who were studied for the type of chimeric BCR-ABL mRNA. Conclusions: This is one of the most recent reported series of CML in children and adolescents from India highlighting the difference in presentation from adults; mainly hepatomegaly, bleeding manifestations, and higher leukocyte count. Presence of b3a3 transcript of p210 breakpoint of BCR-ABL was more common in children (68%) than b2a2 transcript (32%) when compared to adults as recently described in a study from India, which may explain the differences at presentation. [ABSTRACT FROM AUTHOR]

Introduction: The Pediatric Hematolymphoid Disease Management Group (PHL-DMG) at a tertiary cancer care hospital developed extensive patient support programs to improve retention and outcomes while focusing on protocols adapted to meet patient needs. An audit of measures and outcomes was done for a 7-year period from January 2010 to December 2016.Materials and Methods: DMG protocols and patient support activities over the study period were documented and audited. Data was retrieved from internal databases and records. Measures taken and their impact were assessed by descriptive analytical tools. Survival outcomes were calculated using Kaplan-Meier method on SPSS v. 24™ software.Results: Holistic patient support measures were undertaken through a charitable foundation entirely under pediatric oncology. Activities included infrastructure growth, socioeconomic support, provision of accommodation, nutrition, education, and multiple blood component donation drives. Patient registrations increased from 502 in 2009 to 874 in 2016, with the steepest rise in acute lymphoblastic leukemia (ALL) - 330 (2009) to 547 (2016). Treatment refusal and abandonment rates decreased from 32% to 3.4% over the same period, and male to female ratio decreased from 2.56 to 2.28:1. Early mortality in acute myeloid leukemia (AML) fell within 2 years from 26.7% in 2009 to 7%. Five-year overall survival (OS) was 69.5% for all patients registered in 2010, whereas disease-specific 5-year OS was ALL 67.1%, AML 49.3%, chronic myeloid leukemia 100%, Hodgkin lymphoma 90.4%, and non-Hodgkin lymphoma 74.2%.Conclusions: Holistic patient support-specific activities and adapted protocols made a measurable impact on patient outcomes. High survival outcomes of patients have been achieved despite relatively few receiving salvage therapies or stem cell transplant. [ABSTRACT FROM AUTHOR]

The article comments on a research on tyrosine kinase domain (TKD) mutations in chronic myelogenous leukemia (CML) patients in India. It summarizes study findings including imatinib resistance that revealed TKD mutations in CML patients and detection of inhibitory concentration value as determinant of imatinib resistance. Emphasis is given on the significance of log reduction of BCR-ABL tyrosine kinase inhibitor transcript load and assessment of treatment-free remission under clinical trial.

Introduction: BCR-ABL1 kinase domain mutations represent the most frequent mechanism of resistance to tyrosine kinase inhibitor (TKI) therapy, being detected in 40%-50% of imatinib-resistant patients with chronic myeloid leukemia in chronic phase (CML-CP). Over 100 BCR-ABL1 single-point mutations have been reported in patients with imatinib-resistant CML. There were few studies reported from India on BCR-ABL kinase mutations in imatinib failure patients. We present our data on imatinib resistance mutation analysis (IRMA) and use of imatinib dose hike and 2nd-generation TKI at our institute. Materials and Methods: All patients with a diagnosis of CML in a university hospital from June 2003 to July 2016 and who were tested for IRMA in view of imatinib failure, those in CP, and age <18 years were included in the study. Results: A total of 2110 cases of CML reviewed and 269 cases of CML with imatinib failure were analyzed. The male to female ratio was 1.7:1. The median age at presentation was 36 years (range: 18-66 years). Among these, 26% were primary failures and 74% were secondary failures. The treatment was modified either as imatinib dose hike or nilotinib/dasatinib. Molecular response at 12 months was achieved in 25.7% in imatinib dose hike, 46.6% in nilotinib, and 53.8% in dasatinib arms. The 4-year overall survival in mutation detected group was 37.5% and in nonmutated group was 87.7%. Conclusion: Imatinib-resistant mutations were more common in the cases with secondary failure though not statistically significant. T315I mutation was the common mutation found in the study. Imatinib dose hike to the failure cases resulted in optimal hematological response rates. [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]

Context: Tumor progresses through a series of genetic alterations that involve proto-oncogenes and tumor suppressor genes - the gatekeeper, caretakers, and landscaper genes. Microsatellites are short tandem repeat sequences, present over the span of human genome and are known to be variable at multiple loci due to errors in DNA Mismatch Repair machinery.Aim: The present study was aimed to evaluate the association between Microsatellite Instability (MSI) and evolution of Chronic Myeloid Leukemia (CML) - genetically a rare event but profound in this pilot study.Settings and Designs: We explore the possibility of MSI in primary CML patients confirmed by t(9;22) using capillary electrophoresis. Fifteen CML patients and healthy individual samples, respectively, were used to study the markers D17S261 and D3S643.Materials and Methods: The DNA was amplified using tagged and nontagged primers and further subjected to bioanalysis and fragment analysis.Results: While the results from bioanalyzer fluctuated, fragment analysis indicated the presence of microsatellite variability in 80% of the patients' samples as compared to no MSI in normal individuals for both the markers.Conclusion: These findings suggest that MSI is a genetic event that may have a role in CML progression or evolution. Further studies are warranted to understand the plausible underlying causes. [ABSTRACT FROM AUTHOR]

We document the characteristics of BCR-ABL kinase domain mutations (KDM) in the largest study from India comprising of 385 patients and demonstrate that more than half (51.9%) of these patients have detectable abnormalities in the KD both in adult and in pediatric chronic myelogenous leukemia (CML). These comprise singly occurring missense mutations (25.5%), polyclonal/compound point mutations (4.9%), and insertions/deletions (29.6%). Missense mutations were most commonly seen in the imatinib-binding region followed by theP-loop. The commonest mutation in our dataset was T315I. Other common missense mutations were Y253H, M244V, and F317L. A high prevalence of BCR-ABL exon7 deletion (p.R362fs*) was also seen (25.5% of the entire cohort), whereas the 35bpintron-derived insertion/truncation mutation detected in 12 patients. In the pediatric age group, 58.8% of patients harbored missense mutations, polyclonal/compound mutations as well as insertions and deletions. We detected 11 novel mutations (seven missense mutations and four insertions/deletions). [ABSTRACT FROM PUBLISHER]

Circulating megakaryocytic cells abound in chronic myeloid leukemia (CML) seen in India and uniquely provide a setting for observing megakaryocytic maturation in the peripheral blood, a milieu not native to megakaryocytes. Peripheral blood megakaryocytic cells were studied in 324 cases of CML (235 chronic, 65 accelerated and 24 blastic phases). Two maturation themes were evident. Megakaryocytic blasts, especially in some cases of blast crisis, precociously make a foray into platelet formation and end up producing huge agranular or poorly granular cytoplasmic lobulated masses, that break off and come to lie in the circulation. This evidence of unsuccessful effort may exist, in a considerably attenuated form in chronic phase, alongside of the second major theme of megakaryocytic maturation centered around the familiar micromegakaryocyte, characteristic of the chronic phase. This cell is regarded as dysplastic, but produces morphologically normal platelets. The possibility that this occurs via a hitherto unstudied alternative path of platelet maturation that plays out in the peripheral blood, and the contrasting disorderly premature attempt of blasts to form platelets, represent exciting maturation processes that need further study. Our observations fortuitously constitute a revisit of the insightful exposition on the subject by George Minot nearly a century ago. [ABSTRACT FROM AUTHOR]

Introduction: Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome, an abnormally shortened chromosome 22. It is the result of a reciprocal translocation of chromosomes 9 and 22, creating BCR-ABL fusion transcripts, b3a2, b2a2, and e1a2. The aim of our study was to determine the type of BCR-ABL fusion transcripts for molecular diagnosis and investigate the frequency of BCR-ABL fusion transcripts in CML patients by multiplex RT-PCR in CML.Materials and Methods: A single reaction with multiple primers multiplex PCR was used to detect and investigate the type and frequency in 200 CML patients among which 116, 33, and 51 were in CP, AP, and BC phase, respectively.Results: The study included 200 CML patients, among whom breakpoints in b3a2, b2a2 transcripts were detected in 68% and 24%, respectively, while 8% of the patients showed both b3a2/b2a2. A statistically significant difference was seen between frequency of BCR-ABL fusion transcripts and gender (P = 0.03), molecular response (P = 0.04), and hematological response (P = 0.05). However, there was no correlation found between frequencies of BCR-/ABL fusion transcripts and other clinicopathological parameters like age, type of therapy, thrombocytopenia, and white blood cell count.Conclusion: Multiplex reverse transcriptase-polymerase chain reaction is useful and saves time in the detection of BCR-ABL variants; the occurrence of these transcripts associated with CML can assist in prognosis and treatment of disease. [ABSTRACT FROM AUTHOR]

Context: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur.Aim: The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center.Settings and Design: Retrospective study.Materials and Methods: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done.Results: There were 61 such cases (51 males, 10 females). The age range was 7-78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7).Conclusion: Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported. [ABSTRACT FROM AUTHOR]

Context: The exact role of the different transcript variants of BCR-ABL in the pathogenesis of chronic myeloid leukemia (CML) and their impact on prognosis is yet to be definitely enumerated. Aims: In this study, we have tried to correlate the presenting features, risk scores and treatment response with the BCR-ABL variants detected in our patients. Settings and Design: A cross-sectional unicentric hospital-based study on 80 patients diagnosed to have CML by bone marrow cytogenetics and confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Materials and Methods: RT-PCR for BCR-ABL was performed on consecutive patients with CML attending the CML clinic from January 2010 to December 2010.The medical charts of these patients were analyzed after a follow-up of 18 months in a retrospective manner. Statistical Analysis: Box plot and histogram was used to see the distribution of variables. t-test was performed to enumerate the difference between risk scores in two populations of patients carrying two different BCR-ABL transcript variants. Results: Nearly 56.25% of patients had b3a2 (e14a2) while 41.25% of patients showed b2a2 (e13a2) transcripts. The rest 2.5% (two patients) expressed the rare e19b2 variant. Patients with b2a2 presented with higher Sokal, Hasford and European Treatment and Outcomes Study score than their b3a2 counterpart. Different parameters such as the platelet count, leukocyte count, hemoglobin and splenomegaly showed a minor difference between the groups. More patients in the b2a2 group achieved complete hematologic response at 3 months, but it was not significant. Conclusions: Patients with b2a2 variant CML tend to present with higher risk score, but do not behave in a vastly different manner than their b3a2 counterparts. [ABSTRACT FROM AUTHOR]

The prognosis of patients with chronic myeloid leukemia (CML) has changed radically since the advent of imatinib mesylate, a selective inhibitor of BCR-ABL tyrosine kinase. Shortly thereafter, more potent BCR-ABL inhibitors (dasatinib and nilotinib) were introduced for use in patients resistant to or intolerant of imatinib. All three drugs are now approved for initial therapy for chronic phase CML. Response to tyrosine kinase inhibitor (TKI) treatment is assessed with standardized quantitative reverse transcriptase polymerase chain reaction (Q-RTPCR) and/or cytogenetics at 3, 6 and 12 months. Clinical trials have clearly demonstrated that early and deeper cytogenetic and molecular response to TKI therapy is associated with lower rate of disease progression and improved long-term outcomes. In recent times, molecular response as determined by BCR-ABL transcript levels at defined time points is rapidly gaining popularity as a predictive marker for subsequent outcomes in CML. Optimal response is defined as BCR-ABL transcript levels of = 10% at 3 months, < 1% at 6 months, and = 0.1% from 12 months onward while > 10% at 6 months and > 1% from 12 months onward define failure. Patients who do not achieve molecular milestones at 3 or 6 months with 3 months being highly predictive are less likely to achieve cytogenetic responses eventually; early identification of such patients who have a low probability of achieving an adequate response are thus candidates for alternative treatment. Review of literature by electronic search of MEDline, Google Scholar was done using keywords and data was identified and systematically evaluated. [ABSTRACT FROM AUTHOR]

Imatinib is the current gold standard for treatment of chronic myeloid leukemia (CML). Recent pharmacokinetic studies have shown considerable variability in trough concentrations of imatinib due to variations in its metabolism, poor compliance, or drug-drug interactions and highlighted its impact on clinical response. A trough level close to 1000 ng/mL, appears to be correlated with better cytogenetic and molecular responses. Therapeutic Drug Monitoring (TDM) for imatinib may provide useful added information on efficacy, safety and compliance than clinical assessment alone and help in clinical decision making. It may be particularly helpful in patients with suboptimal response to treatment or treatment failure, severe or rare adverse events, possible drug interactions, or suspected nonadherence. Further prospective studies are needed to confirm relationship between imatinib plasma concentrations with response, and to define effective plasma concentrations in different patient populations. [ABSTRACT FROM AUTHOR]

All India Institute of Medical Sciences, New Delhi is an Apex Institute and caters to more than 1.5 million out-patients and 80,000 in-patients every year. In this study, we have presented data of patients over a period of 20 years. This encompasses our initial experience with hydroxyurea, then interferon alone or with cytarabine and finally imatinib. We have presented data of 525 patients treated on imatinib alone. Imatinib dose was increased in 56 (10.6%) patients and regain of complete hematological response was seen in 26 patients. A total of 14 patients were transplanted for different indications of chronic myeloid leukemia and out of which 12 patients are doing well, while two died due to Grade IV gut graft-versus-host disease. [ABSTRACT FROM AUTHOR]

Background: Chronic myeloid leukemia (CML) is the commonest hematological malignancy in India. This manuscript is a single center analysis CML in chronic phase (CP). Materials and Methods: We did retrospective analysis of almost 1000 patients registered as chronic myeloid leukemia over a period of 6 years at Tata Memorial Hospital. Results: We found striking difference in cytogenetic response among patients presenting in late chronic phase (CP) compared with the patients in early CP. The rate of complete cytogenetic response among patients in late CP was 60% while in early CP it was 80%, which was statistically significant (P = 0.0001). The overall survival was 86%, at a median follow-up of 51 months. Innovator glivec was taken by 671 patients among which complete cytogenetic response (CCyR) was seen in 72% whereas generic veenat was taken by 237 patients and CCyR was seen in 75% of them. Conclusion: Availability of imatinib has dramatically changed the outlook for CML in India. The response was identical for those treated with innovator brand of imatinib as compared to the generic brand. Hence quality generics provide a cost effective solution, which is particularly relevant in the current global scenario. [ABSTRACT FROM AUTHOR]

In an effort to collaborate the data of chronic myeloid leukemia (CML) patient from all over India, meeting was conceived by ICON ( Indian Cooperative Oncology Network) in 2010. This article presents the summarized picture of the data presented in the meeting. In the meeting 8115 patients data was presented and 18 centres submitted their manuscripts comprising of 6677 patients. This data represents large series of patients from all over the country treated on day to day clinical practice and presents the actual outcomes of CML patients in India. The compilation of data confirms the younger age at presentation, increased incidence of resistance and poor outcomes in patients with late chronic phase. It also addresses the issues like Glivec versus Generic drug outcomes, safety of Imatinib during pregnancy and mutational analysis among resistant patients. It concludes that survival and quality of life of CML patients in India has improved over the years especially when treated in early chronic phase. The generic drug is a good option where original is unable to reach the patient due to various reasons. Hopefully, this effort will provide a platform to conduct systematic studies in learning the best treatment options among CML patients in Indian settings. [ABSTRACT FROM AUTHOR]