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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Expression of Aberrant Markers and its Association with Remission Postinduction Therapy in Acute Lymphoblastic Leukaemia and Acute Myeloid Leukaemia
Correspondence Address :
Linu Abraham Jacob,
Professor, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Hombegowda Nagar, Bengaluru, Karnataka, India.
E-mail: kmiolinu@gmail.com
Introduction: Haematological malignancies contribute to a significant number (8.2%) among cancer patientsin India. Bursa-Acute Lymphoblastic Leukaemia (B-ALL), Thymus-Acute Lymphoblastic Leukaemia (T-ALL) and Acute Myeloid Leukaemia (AML) are the three main types of leukaemias distinguished based on flow cytometry. Expression of Cluster of Differentiation (CD) markers of a lineage distinct to the blast population is termed as aberrant expression (expression of B/T cell markers in AML or myeloid markers in ALL). Role of aberrant marker expression in leukaemias remain an enigma till date. Aberrant expression of antigens may be associated with adverse outcomes.
Aim: To study the expression of aberrant markers and their association with the remission status postinduction therapy in ALL and AML.
Materials and Methods: A retrospective cross-sectional study done accessing the medical records of Acute Leukaemia patients admitted from 1st January 2019 to 31st December 2019 at Kidwai Memorial Institute of Oncology, Bengaluru. A total of 144 cases were included of which 86 cases were of AML and 58 cases were ALL. ALL was further divided into B-ALL and T-ALL with 40 and 18 cases respectively, 18 cases of T-ALL and 86 cases of AML were included. Demographic and clinicohaematological parameters were recorded. All quantitative variables were described as Mean {Standard deviation(SD)} and all qualitative variables were depicted as number (proportion). Statistical significance assessed by Chi-square and Fischer-Exact test using Statistical Package for the Social Sciences (SPSS) version 22.0.
Results: Majority of patients belonged to 16-25 years age group with a male preponderance of 58.3%. Aberrant marker expression was associated with the remission status with a p-value of 0.23 and 0.185 in ALL and AML patients respectively and was statistically not significant. While the Chi-square test when applied to the total cases (both ALL and AML combined) the p-value was 0.03 and statistically significant.
Conclusion: Aberrant marker expression might predict poor response to induction therapy in acute leukaemias. However, larger studies are needed to confirm these results.
Antigens cluster of differentiation, Haematologic neoplasms, Remission induction, Treatment failure
Haematological malignancies contribute to a significant number (8.2%) of cancer patients in India (1). They have been recognised and treated as a distinct entity since the beginning because of their differences in aetiopathogenesis, genetics, clinical features, prognosis and response to treatment (2),(3). The prevalence of clinically meaningful haematological neoplasm subtypes lacks clarity owing to complexity of patterns reporting as compared to other cancers (4). In spite of the progress achieved in the cancer care treatment in other malignancies, the additions to the treatment armamentarium in haematological malignancies still remain only a handful (5),(6).
Leukaemias are due to a defect in the process of differentiation of blood forming elements of lymphoid or myeloid lineage (7). Different Cluster of Differentiation (CD) markers are expressed at different stages of development on both lymphoid and myeloid lineage cells (8). The identification and immunophenotyping of these markers by flow cytometry helps in both diagnosis and classification of leukaemias (9). The EGIL (European Group for Immunological Characterisation of Acute Leukaemias) (10) or World Health Organisation (WHO) criteria is used to characterise blasts on the basis of markers associated with B-cell, T-cell, and myeloid lineages depending on how strongly they are associated with a specific lineage (11).
B-Acute Lymphoblastic Leukaemia (ALL), T-ALL and Acute Myeloid Leukaemia (AML) are the three main types of leukaemias distinguished based on flow cytometry. Mixed Phenotypic Acute Leukaemia (MPAL) is another distinct entity where CD markers of more than one lineage are expressed in a single blast population or two discrete populations (10). Expression of CD markers of a lineage distinct to the blast population is termed as aberrant expression (expression of B/T cell markers in AML or myeloid markers in ALL). Aberrant marker expression may be due to underlying genetic causes (12).
MPAL has a worse prognosis compared to other leukaemias. This is thought to be due to the presence of two different lineage markers. The treatment aimed at one of the lineages might lead to the evolution of blasts of the other lineage. Poor responders are sometimes switched from AML to ALL directed therapies or vice versa and some patients achieve complete response (10),(13),(14).
Role of aberrant marker expression in leukaemias remains an enigma till date. Aberrant expression of antigens may be associated with adverse outcomes (12). The authors aimed to study the expression of aberrant markers and their association with the remission status post induction therapy in ALL and AML. The study may lead to identification of poor prognostic biomarkers that may lay foundation for the development of targeted therapies in the future.
This was a retrospective cross-sectional study done accessing the medical records of patients admitted from January 1, 2019 to December 31, 2019 in leukaemia wards of Kidwai Memorial Institute of Oncology, Bengaluru, India. The study was approved under Institutional Scientific Review Board and Institutional Ethical Committee. (No: KCI/MEC/010/20.August.2019). Informed written consent was obtained from all participants.
Inclusion criteria: Forty cases of B-ALL, 18 cases of T-ALL and 86 cases of AML were identified and included for the study in accordance with the EGIL criteria (10).
Exclusion criteria: All those cases of acute leukaemias, which were not in accordance with the EGIL, and AML-M3 cases were excluded from the study.
Details of age, performance status, haemogram and biochemical parameters at the time of presentation, cytogenetics, treatment regimen used and status of remission post induction were documented. Flow cytometry details and expression of aberrant markers were noted in each case. Flow cytometry was done using a 10 colour, 3 lasers Navios Ex (Beckman Coulter) instrument by a CD45 gating strategy. Antibodies used were CD34, CD1a, CD2, cCD3, CD4, CD5, CD7, CD8, CD19, CD10, CD20, cCD79a, CD117, MPO, CD13, CD33, HLA-DR, CD64, CD11c, CD14 and CD184.
Statistical Analysis
Descriptive and inferential statistical analysis was carried out. Results on continuous measurements were presented as Mean±SD (minimum-maximum) and results on categorical measurements were presented in Number (%). Significance was assessed at 5% level of significance. Chi-square/Fisher-Exact test was used to find the significance of study parameters on categorical scale between two or more groups, nonparametric setting for qualitative data analysis. Fisher-Exact test/Chi-square test with Yates's correction was used when cell samples were very small. The p-value <0.05 was considered significant. The statistical software namely SPSS version 22.0 and R environment version 3.2.2 were used for the analysis of the data.
Majority of patients of ALL (70% B-ALL and 61% T-ALL) were adolescents and belonged to the age group 16-25 years; whereas majority of patients of AML belonged to 16-25 years (35%) and 36-45 years (23%). There was a male predominance in all the three types (55% in B-ALL, 88.9% in T-ALL and 53.5% in AML). Age and sex wise distribution of patients shown in the (Table/Fig 1), (Table/Fig 2).
Most of the ALL patients presented with either a pancytopenia or a bicytopenia (anaemia+thrombocytopenia) with normal leukocyte counts while most of the AML patients were with bicytopenia and elevated leukocyte counts at diagnosis. Laboratory parameters are shown in the (Table/Fig 3), (Table/Fig 4).
Cytogenetic results are detailed in the (Table/Fig 5). A 66 (76.7%) of AML patients had normal karyotype, three patients had a complex karyotype, three patients had t(8;21) and rest had either failed cytogenetics or translocations of undetermined significance. Breakpoint Cluster Region protein (BCR) ABL genes was not done in all patients of B-ALL. However, two cases showed Philadelphia chromosome positivity on conventional karyotyping were given Tab. Imatinib in addition to chemotherapy during induction phase.
Majority (38) of patients received Berlin-Frankfurt-Munich (BFM) 95 protocol, one patient BFM 90 and one patient GMALL protocol for induction treatment of B-ALL. All patients of T-ALL received BFM 95 protocol. Treatment protocols used for AML patients were 3+7 induction, hypomethylating agents and low dose Cytarabine and shown in (Table/Fig 6).
Among B-ALL 36 (90%) of patients achieved remission by the end of induction treatment while 2 (5%) patients died and 2 (5%) patients failed to achieve remission. 16 (88.9%) patients of T-ALL achieved remission while 1 (5.6%) patient died and 1 (5.6%) patient failed to achieve remission. While in AML, 49 (57%) patients achieved remission, 6 (7%) died, 12 (14%) defaulted treatment and 19 (22%) patients failed to achieve remission. Among those who achieved remission 35 (71%) patients received 3+7 induction therapy, 14 (28.5%) patients received hypomethylating agents (Four cycles Azacitidine/Decitabine) and none received Low Dose Ara-C (LDAC).
Overall 14 (35%), 6 (33%) and 34 (39.5%) number of patients had aberrant CD markers in B-ALL, T-ALL and AML respectively. Most common aberrant markers expressed in B-ALL were CD33, in T-ALL were CD10 and in AML were CD7 and CD19 as shown in the (Table/Fig 7). In patients who achieved remission aberrant CD markers were expressed in 12 (85.7%), 4 (66.7%) and 20 (58.8%) patients of B-ALL, T-ALL and AML respectively. In those who failed to achieve remission aberrant markers were expressed in 2 (14.3%), 1 (16.7%) and 10 (29.4%) patients of B-ALL, T-ALL and AML, respectively. Interpreting in another way in patients of B-ALL, T-ALL and AML who expressed aberrant CD markers remission was achieved in 12 (85.7%), 5 (83.3%) and 20 (58.8%) number of patients; and in those who didn’t express aberrant markers remission was achieved in 24 (92.3%), 12 (100%) and 29 (55.8%) number of patients as shown in the (Table/Fig 8), (Table/Fig 9). Aberrant marker expression was associated to the remission status with a p-value of 0.23 and 0.185 in ALL and AML patients, respectively and was statistically not significant. While the Chi-square test when applied to the total cases (both ALL and AML combined) the p-value was 0.03 and statistically significant.
In the present study, out of the total 144 cases, 86 cases were AML and 58 cases were ALL. ALL was further divided into B-ALL and T-ALL with 40 and 18 cases respectively. AML was categorised according to French-American-British (FAB) grouping and majority cases were M2 and M4 (41 and 33, respectively). AML-M3 was excluded from the study. The present case case profile is similar to that reported by Sherrer RT et al., and Salem DA and Abd El-Aziz SM while in contrary to Gujral S et al., and Chaudhary A et al., who reported majority of cases as ALL (15),(16),(17),(18). Complete blood count and karyotyping results were well in accordance with the usual presentation in acute leukaemias patients as per conventional data (19).
The adherence to treatment was excellent in ALL patients and could be explained by both young age at presentation and a good performance status, while 14% of AML patients defaulted treatment. Authors would infer this as a result of poor performance status at the time of diagnosis. The fact that all the defaulted patients were on LDAC treatment supports authors inference as this treatment is generally reserved for patients with poor performance status.
Remission rates of the present study patients were well within the expected rates (20),(21). Around one-third of patients had one or more aberrant marker expression. Most common aberrant markers expressed were CD33, CD10 and CD7/CD19 in B-ALL, T-ALL and AML, respectively. These results of aberrant marker expression contradict the results of Chaudhary A et al., but agree with that of Momani A et al, (18),(22).
Correlation of aberrant marker expression was not statistically significant when assessed independently for each of the three types of acute leukaemia. However, when the statistical test was performed for the total number of patients included in the study irrespective of their leukaemia subtype the p-value was 0.03 and was statistically significant. In spite of the well-known biological and prognostic differences between the different types of leukaemias, authors would like to infer these results as a probable contribution of increased sample size on the prediction of significance. In future, well-structured studies and studies with larger sample sizes can give more reliable answers are hoped.
Limitation(s)
Limitations of the present study include; firstly, it was based on cross-sectional data and authors couldn’t account for the missing information. Secondly, Philadelphia positivity was not assessed in all B-ALL patients which might influence the remission results largely. Thirdly, molecular typing was not done in most of the AML patients due to financial constraints and hence patients could not be risk stratified as per standard guidelines. Lastly, the present sample size was limited and might have interfered with the results as authors sometimes encountered a cell sample size <5 during comparison tests.
Nearly one-third of patients had one or more aberrant marker expression. Most common aberrant markers expressed were CD33, CD10 and CD7/CD19 in B-ALL, T-ALL and AML, respectively. Aberrant marker expression might predict poor response to induction therapy in acute leukaemias. However, larger studies are needed to confirm these results. Studies looking into aberrant marker expression and early relapse might further help in understanding its impact on prognosis.
10.7860/JCDR/2021/48201.15139
Date of Submission: Dec 20, 2020
Date of Peer Review: Mar 03, 2021
Date of Acceptance: May 17, 2021
Date of Publishing: Jul 01, 2021
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
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