scholarly journals Chronic Myeloid Leukemia in Adolescents and Young Adults Treated with Generic Form of Imatinib in Resource Limited Setting: A Single Center Experience from Myanmar

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5451-5451
Author(s):  
Yin Nwe Han ◽  
Aye Aye Gyi ◽  
Khin Thida Htut
Keyword(s):  
Young Adults ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Female Ratio ◽  
Resource Limited ◽  
One Year ◽  
Male To Female ◽  
Limited Setting

Abstract Chronic myeloid leukemia (CML) is an acquired myelo-proliferative disorder characterized by the presence of BCR-ABL1 fusion transcript with deregulated tyrosine kinase activity. Leukemias are one of the leading causes of cancer related deaths in adolescents and young adults (AYA) particularly in resource limited countries. Recent democratic government in Myanmar holds supportive policies for treatment of cancers in younger population and subsidizes some therapies including imatinib mesylate, a selective BCR-ABL 1 tyrosine kinase inhibitor, although there is still limitation for cytogenetic and molecular monitoring of therapy. This study on response to imatinib in newly diagnosed chronic phase CML was carried out during January 2016 to February 2018 at the North Okkalapa General and Teaching Hospital of Yangon, Myanmar where molecularly confirmed new CML in chronic phase were treated with generic form of imatinib bought by hospital tender system, Unitinib (United Biotech (P) ltd. India) followed by cytogenetic analysis of bone marrow and molecular detection of BCR-ABL1 transcript from peripheral blood by in house real time PCR machine at one year. They are divided into AYA (aged 15-39 years) and adult age groups (40 years and older) and clinical parameters and response to treatment with imatinib 400mg per day were compared. Among 56 cases (median age of 39.5 years, male to female ratio of 1.5:1), half were AYA (28 of 56) with median age of 28.5 years compared to 50 years in adult group with higher male to female ratio of 3.6:1 in AYA group. Patients in AYA had larger spleen size (11 vs 5.5 cm) and higher median white cell count compared to adults (366 x 109/l vs 224 x 109/l) although initial platelet count, peripheral blood eosinophil, basophil and blast percent and Sokal score were comparable. Additional chromosomal abnormalities were detected in 2 AYA and 3 adults with CML. There was no difference in complete haematologic response at 3 and 12 months between AYA and adults (96.4% vs 96.4% and 92.9% vs 89.3% respectively). At 12 months, complete cytogenetic response of AYA at 67.9% was less than 75.0% of adults, it was statistically not significant. Using in house molecular method although not standardized, 14.3% of AYA and 32.1% of adults were molecularly undetectable at one year. The response of AYA to imatinib in this study was comparable to adults despite having adverse prognostic features and receiving only generic forms of treatment in resource limited setting and it would further help support from authorities for leukemia in younger population. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Retrospective Cohort Study of Upfront Nilotinib in Chronic Myeloid Leukemia: A Single-Center Experience

2021 ◽  
Author(s):  
Reema Singh ◽  
Jyotsna Kapoor ◽  
Rayaz Ahmed ◽  
Pallavi Mehta ◽  
Vishvdeep Khushoo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Elevated Serum ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Female Ratio ◽  
Single Center Experience ◽  
Male To Female

Abstract Context Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Aims We aim to evaluate the responses and safety of upfront Nilotinib therapy in Indian CML patients. Setting and Design We retrospectively reviewed the medical records of CML patients who received Nilotinib as an upfront treatment at our center between January 1, 2011 and October 15, 2019.The follow-up was taken till March 31, 2020. Results Forty One patients (n = 36 chronic phase and five accelerated-phase CML) received frontline Nilotinib. Median age was 39 years (21–63) with male-to-female ratio of 1.1: 1. At 3 months, 96.9% patients achieved BCR-ABL of ≤10% at international scale. By the end of 12 months, 71.5% patients achieved major molecular response (BCR-ABL ≤0.1%) and 91.4% patients achieved complete cytogenetic response assessed by BCR-ABL polymerase chain reaction of ≤1%. Common toxicities observed were weight gain, thrombocytopenia, corrected QT prolongation, and elevated serum amylase in 14 (34.1%), 7(17.07%), 4(9.7%), and 4(9.7%) patients, respectively. Overall, five patients had loss of response with further progression and death in three patients. At a median of 43.7 months, 38 patients survived with estimated 3 year event-free survival and overall survival of 65 ± 9 and 93 ± 5%. Conclusion This study showed remarkable good response with upfront Nilotinib in Indian patients with CML.

scholarly journals Immunophenotyping in Chronic Myeloid Leukemia Blast Crisis: Looking beyond Morphology

2016 ◽  
Vol 50 (4) ◽  
pp. 181-184
Author(s):  
Subhash Varma ◽  
Neelam Varma ◽  
Pankaj Malhotra ◽  
Vikram Narang ◽  
Man US Sachdeva ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Common Occurrence ◽  
Treatment Protocols ◽  
Female Ratio ◽  
Leukemia Blast ◽  
Male To Female

ABSTRACT Introduction Patients of chronic myeloid leukemia (CML) eventually transform to blast crisis (BC) after a variable length of chronic phase (CP). With improvement in management protocols, many patients of CML-BC are expected to show remission after initial chemotherapy and a better survival. Hence, it becomes imperative to correctly classify the nature of BC for further course of management. Materials and methods This study retrospectively analyzed cases of CML-BC, over a period of 5 years, with comprehensive immunophenotyping done on flow cytometry. Results Fifteen cases of CML-BC with male-to-female ratio of 3:1 and mean age of 40.2 years were included in the study. Flow cytometry revealed 14 cases of myeloid and one case of lymphoid BC. One case each of megakaryocytic and myelomonocytic lineage were seen among the 14 cases of myeloid BC. Aberrant marker expression was a common occurrence. Myeloperoxidase cytochemical stain had shown positivity only in 3 of the 14 cases of myeloid BC. Conclusion Immunophenotyping is necessary for assigning specific lineage to blasts in patients of CML-BC and thus providing clinically useful information regarding the treatment protocols and prognosis of the patient. How to cite this article Narang V, Sachdeva MUS, Bose P, Varma N, Malhotra P, Varma S. Immunophenotyping in Chronic Myeloid Leukemia Blast Crisis: Looking beyond Morphology. J Postgrad Med Edu Res 2016;50(4):181-184

Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

2018 ◽  
Vol 140 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Fiorina Giona ◽  
Michelina Santopietro ◽  
Giuseppe Menna ◽  
Maria Caterina Putti ◽  
Concetta Micalizzi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Real Life ◽  
Chronic Phase ◽  
Optimal Management ◽  
Molecular Monitoring ◽  
Italian Experience ◽  
Adults And Children

Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.

Molecular Response to Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML), the Experience At Tawam Hospital, Abudhabi, UAE

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4458-4458
Author(s):  
Arif Alam ◽  
Sabir Hussain ◽  
Amar Lal ◽  
Donna Lee ◽  
Jorgen Kristensen
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Technique ◽  
Molecular Response ◽  
Female Ratio

Abstract Abstract 4458 Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a balanced reciprocal translocation involving the long arms of chromosomes 9 and 22. The fusion gene that is created by this translocation (BCR-ABL1) encodes for a constitutively active protein tyrosine kinase that is primarily responsible for the leukemic phenotype. Targeted therapy with Tyrosine Kinase Inhibitors (TKIs) has become the recommended first-line treatment for patients with CML. Monitoring of the CML is done with quantification of the BCR-ABL transcripts by RQ-PCR–based molecular technique. Twenty nine patients were diagnosed with CML in chronic phase between January 2009 till June 2012. The median age was 32 years (range 22–68 years). Male to female ratio was4.14:1. Three patients were lost from follow up after diagnosis and are excluded. Molecular response is available for 16 patients. Nine patients were treated with Imatinib 400 mg daily, four with Dasatinib 100 mg daily and three with Nilotinib 400 mg BID daily as upfront therapy. Twelve patients have achieved MMR/CMR (75 %) within 18months of starting therapy. Four patients have failed to achieve MMR by 24 months. All non responders were on Imatinib. Interestingly six (37.5%) patients achieved MMR/CMR within 9 months of starting TKIs. Of these only 1 was on Imatinib while the rest were on 2nd generation TKIs (Nilotinib 3 and Dasatinib 2). MMR report from Enestnd trial is 67–71% in favor of Nilotinib as compared to Imatinib 44%, while the Dasision trial reported a MMR of 44 % in favor of Dasatinib with faster rate to response. Our results mirror the results of these phase 3 randomized trial with MMR/CMR of 75 %. Until today there has been no case of progressive disease. Our data is limited but shows that the median age is much lower compared to Western countries, just reflecting differences in the age distribution of the population in the UAE with 80% being below the age of 65 years. Expatriates accounts for approximately 80% of the population in the UAE and many are temporary employed, having limited health care coverage, limited financial means as well as limited possibilities to attend regular follow-ups. This leads to compliance problems, loss from follow-up and suboptimal management and monitoring of their disease. Disclosures: Alam: BMS/Novartis: Consultancy, Honoraria. Hussain:BMS: Consultancy, Honoraria.

Consistency Of RQ-PCR Analysis Results In Peripheral Blood and Bone Marrow Samples In Chronic Myeloid Leukemia Patients: Relevance From The Practical and Logistic Point Of View

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2592-2592
Author(s):  
Giovanna Rege-Cambrin ◽  
Carmen Fava ◽  
Enrico Gottardi ◽  
Filomena Daraio ◽  
Emilia Giugliano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Wilcoxon Test ◽  
Molecular Response ◽  
Two Samples ◽  
The Mean

Abstract Background Consensus has been achieved that standardized molecular quantitative analysis (RQ-PCR) on peripheral blood (PB) is a suitable method for monitoring residual disease in chronic myeloid leukemia (CML). However, BM is still obtained at specific timepoints, and in a number of cases, only bone marrow (BM) sample collected for cytogenetic analysis is available. Being one of the laboratory involved in the standardization process of molecular monitoring for CML patients, we decided to perform a comparative analysis of BM and PB samples in order to evaluate the consistency of the results. Methods Between March 2009 and January 2013, 230 consecutive RQ-PCR tests to assess BCR-ABL transcript levels from simultaneously collected PB and BM samples were performed (for a total of 460 analysis) on 77 patients affected by Ph+ CML in chronic phase treated in our center. All samples were analyzed in the same laboratory following international guidelines (Cross N, Leukemia 2012) and results were expressed according to the International Scale; ABL1 was used as control gene. Time from blood-drawn to processing was within 3-4 hours. Results Among the 230 pairs, 3 were considered as not evaluable because of inadequate material; for the purpose of this study, the remaining 227 pairs were considered as “evaluable”. 204 pairs were classified as “fit” when both BM and PB ABL amplification resulted in more than 10.000 copies; 23 pairs were considered unfit for ABL1 <10.000 in either one of the two samples (21) or both (2). The mean number of ABL1 copies in all evaluable samples was 35.639 for BM (SD 21.465) and 30.958 for PB samples (SD 18.696). Correlation analysis was performed on the whole population and in 4 subgroups: No Complete Cytogenetic Response (CCyR, 22%), CCyR without Major Molecular Response (MMR), (21.6%), CCyR with MMR (excluding patients with MR4 or better,19.8%), and CCyR with MR4 – MR4.5 (32,6%). Cytogenetic response was not available in 9 BM samples (4%), not included in the subgroup analysis. Spearman correlation of BCR/ABL ratio values between PB versus BM paired samples resulted in a statistically significant correlation in all groups, both for evaluable and fit pairs. Correlation was stronger in samples that were not in MMR or better (table 1 and figure 1). The Wilcoxon test showed that the mean difference of BCR/ABL values between paired PB and BM samples was not significantly different from zero (in evaluable and fit pairs by considering the whole population). Concordance was further analyzed by the K test which resulted in a coefficient equal to 0.627, corresponding to a notable degree of concordance. For patients in CCyR, agreement on classification of response (MMR, MR4, MR4.5) between paired PB and BM samples was observed in 125/168 evaluable pairs; 22 out of the 43 evaluable cases of disagreement were due to technical failures (in 10 BM and 12 PB samples). In 14 of the remaining 21 cases, PB was more sensitive. Conclusions In a single center experience of molecular analysis, BCR/ABL ratio was highly consistent in BM and PB samples. In less than 10% of the cases a single test did not reach the required sensitivity of 10.000 ABL copies and the double testing allowed to obtain a valid result. This may be especially valuable in evaluating an early response (i.e. at 3 months), when the amount of disease has prognostic relevance. The analysis will be expanded to include samples coming from different centers to evaluate a possible role of timing and transport on data consistency. Disclosures: Saglio: Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals Baseline Tryptase Levels Correlate with Baseline Basophil Levels in Chronic Myeloid Leukemia-Chronic Phase

2020 ◽  
pp. 171-176
Author(s):  
Anisha Mathew ◽  
Manisha Naithani ◽  
Sarama Saha ◽  
Rituparna Chetia ◽  
Uttam Kumar Nath
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Surrogate Marker ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Serum Tryptase ◽  
Baseline Serum ◽  
Tryptase Level ◽  
Blood Basophil

Aims: To study whether there is any correlation between baseline blood basophil count and serum tryptase levels in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP) patients. Settings and Design: 40 newly diagnosed CML-CP patients were enrolled from Medical Oncology Hematology OPD based on their baseline BCR-ABL status (done in department of Biochemistry). Methods and Materials: Serum tryptase level was measured using Sandwich ELISA and peripheral blood basophil count was estimated using automated cell counter & peripheral blood film examination. BCR-ABL quantification was done using real time PCR after conversion of RNA (extracted from whole blood) to cDNA. Statistical Analysis Used: SPSS Version 23. Results: Baseline peripheral blood basophil levels showed a significant correlation with baseline serum tryptase levels (p<0.01) and tryptase level also correlated with EUTOS score, which has basophil count as one of the parameters. This may signify that serum tryptase levels can be a surrogate marker of the basophil compartment in CML-CP. Conclusions: Based on findings of the present study and other studies available in literature, serum tryptase can be utilised as a surrogate marker of the basophil compartment in CML-CP.

scholarly journals EFFICACY OF NILOTINIB IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

2019 ◽  
Vol 10 (4) ◽  
pp. 1-4
Author(s):  
Sajid Ali ◽  
Tahir Mehmood ◽  
Kausar Bano ◽  
Muhammad Akram et al.
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Guidelines ◽  
Ph Value ◽  
Standard Dose ◽  
Chronic Phase ◽  
Current Treatment ◽  
Female Ratio ◽  
The Mean ◽  
Stage Renal Disease

ABSTRACT:MATERIAL AND METHODS: This study was conducted on 92 diagnosed cases of chronic myeloid leukemia at Department of Oncology, Jinnah Hospital Lahore from August 2016 to January 2017. Patients from either gender, between the ages of 20 to 60 years were included in the study while patients having diabetes and end stage renal disease with glomerular filtration rate less than 15 ml/min were excluded. Nilotinib treatment with the standard dose (300 mg twice daily) was given to patients with chronic phase of chronic myeloid leukemia (CP-CML). Patients were monitored as recommended by the current treatment guidelines. Treatment outcome of CP-CML in terms of efficacy was assessed at the end of 6 months of treatment.OBJECTIVE: To determine the efficacy of nilotinib in patients of chronic myeloid leukemia, chronic phase, in terms of detection of BCR-ABL by FISH method. RESULT: The mean age of the patients was 38.84 ± 11.67 years, with male to female ratio of 1.04:1. The mean PH value of the patients was 17.05 ± 18.53 and efficacy was achieved in 36 (39.13%) patients. CONCLUSION: The efficacy of nilotinib was achieved in significant number of CML patients.

Comparative study of safety and efficacy of imatinib mesylate therapy in pediatric and adult chronic myeloid leukemia

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20016-20016
Author(s):  
N. Raizada ◽  
T. Sagar ◽  
S. Ramanan
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dropout Rate ◽  
The Body ◽  
Imatinib Resistance ◽  
Hematopoietic Stem ◽  
Female Ratio

20016 Background: Chronic Myeloid Leukemia (CML) is one of the rare pediatric cancers. Imatinib is now the standard of care in adult CML (ACML) with newer compounds being investigated to overcome the burden of Imatinib resistance. Pediatric CML (PCML) has been an area little explored and effective strategies are not yet defined. Although, allogenic hematopoietic stem cell transplantation (HSCT) still remains the gold-standard treatment, the choice of drug in the subset in which HSCT is not a suitable option remains to be determined. Methods: This was a single-institution prospective study conducted from April 2004-March 2006, analyzing and comparing 293 Philadelphia chromosome (PH) positive CML patients in pediatric and adolescent subsets (i.e. age =18 years) not eligible for allogenic HSCT with ACML. After obtaining a written informed consent, a starting dose of 400 mg/m2/d Imatinib mesylate was administered in adults, whereas in pediatric and adolescents it was 400 mg/m2/d if the body surface area (BSA) was <1 m2, or 400 mg/d if BSA was >1m2. Results: 27 patients were in the age group =18 years; male to female ratio was 1.07:1. Gender ratio in 266 ACML patients showed a male preponderance (2.5:1). The mean age in ACML was 37.4 years. In pediatric subsets, a trend toward CML in adolescents was observed with mean age 14.85 years. Majority of the patients were in chronic phase (81.5% PCML and 85.7% ACML) with overall 93% patients receiving prior hydroxyurea as a cytoreductive agent. An unusual finding was higher incidence of Hypodiploidy (significance undetermined) and 5 patients had double PH. 80.1% ACML patients achieved complete hematological response, but it was significantly lower (59.3%) in PCML. 39.5% ACML achieved major cytogenetic response which was less than most published western data. Hematologic and non-hematologic toxicities (GI, dermatological etc) were found to be higher in ACML. Low toxicities in PCML were attributed to good tolerance to Imatinib therapy; however a higher dropout rate in pediatric subsets was possibly due to poor social and parental support. Conclusion: We conclude that imatinib mesylate is both safe and efficacious drug for ACML, however further research is warranted in pediatric and adolescent population to establish its efficacy. No significant financial relationships to disclose.

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