Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
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Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Lucknow
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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
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An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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.
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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

Important Notice

Original article / research
Year : 2008 | Month : June | Volume : 2 | Issue : 3 | Page : 838 - 842

Effects of Clinical, Haematological and Immunophenotyping Factors on the Prognosis of Acute Promyelocytic Leukaemia (APL) at the Tabriz Haematology and Oncology Research Centre

KERMANI I A*, KERMANI T A**, KERMANI A A***, DOLATKHAH R****

*Professor of Hematology and Medical Oncology, Hematology and Oncology Research Center, Tabriz University of Medical Sciences.**MD, Tabriz University of Medical Sciences.***Medical student, Medical Faculty Tabriz University of Medical Sciences.****MD, Hematology and Oncology Research Center, Tabriz University of Medical Sciences The name of the department(s) and institution(s):Hematology and Oncology Research Center, Tabriz University of Medical Sciences

Correspondence Address :
Iraj Asvadi Kermani MD, Hematology and Oncology Research Center, Tabriz University of Medical Sciences,Ghazi Tabatabai Hospital, Daneshgah Ave, PO Box: 5166614731 Tabriz/ IR Iran. Email address: iraj_akermani@hotmail.com Tel/Fax: +98 0411 3343844

Abstract

Background: Acute Promyelocytic Leukemia is one of AML subgroups that is high lighted by coagulopathy and different mode of treatment. It is specified by district cell morphology and immunophenotyping characteristics.
Aims: The aim of this study was evaluation of the effects of cytologic , clinical and biologic factors specially CD34 expression in prognosis in APL patients.
Materials and Methods: In a Descriptive retrospective analysis the files of 60 APL patients reviewed and the extracted data's statistically analyzed using SPSS soft ware with Chi Square and T- test.
Results:Dislike references complete remission and disease free survival (DFS) had no significant correlation with age, sex, WBC, Hb, platelet count, purpura, CD34 status, and percent of Blasts in bone marrow. There was no significantly statistical correlation between CD34 expression with morphology, age, sex, WBC, platelet count, percent of BM blasts and purpura. Cases with CD34 expression had sever anemia (5.8± 1.08) in comparison with CD34 negative APLs (P=0.020).
Conclusion:In spite of the influence of known prognostic factors on prognosis, results of our study were not concordant with references, therefore it is logical to think that in APL there should be different prognostic factors .Failure in obtaining complete remission in all CD34+APLs cases may be the cause of poor prognosis of CD34 positively in these patients and needs further studies for better clarification.

Keywords

Acute Promyelocytic Leukemia, CD34, Complete Remission, Disease Free Survival.

Introduction
Acute Promyelocytic Leukaemia (APL) is characterized by typical promyelocytes and coagulopathy that result in severe haemorrhage, which accounts for about 10% of adult acute myeloid leukaemia (1). It is the cause of 46-80% early deaths (2),(3),(4), and is characterized by the Promyelocytic Leukaemia-Retinoic Acid Receptor α(PML-RAR α) fusion gene (1).Besides cellular morphology, genetic translocation t(15;17)(q22,q12) and specific immunophenotyping (CD13+ ,CD33+ ,CD14- ,CD9+,HLADR- ,CD4-) are necessary for confirming diagnosis (2,4,5,6) Most of the cases developed excellent prognosis after they entered complete remission (CR) (85-90%) using All- Trans Retinoic Acid(ATRA) with or without antracyclin chemotherapy (7). It is believed that different clinical and biological parameters such as age, number of White Blood Cells (WBC) and purpura affect Complete Remission and survival rate. A lower age group (<30 years), a WBC count of <1000/μl, and absence of purpura have a positive effect on early development of CR and higher survival (7),(8). Pancytopenia is the most common finding in APL, although the white blood cell count was elevated in 10-30% of patients (9). Moreover, recent studies reported that CD34 surface expression is associated with poor clinical outcome in patients with APL. Despite all these data, the issue of CD34 expression in APL remains unsolved (10).
Regarding the high incidence of APL in our district (11), with respect to the possible ecological issues on its biology and different therapy responses (personal observation), we studied CD34 expression on promyelocytes of APL cells, its relationship with complete remission and disease free survival (DFS) rate, and other clinical factors (except cytogenetics) as prognostic factors, at the Haematology and Oncology Research Center of the Tabriz University of Medical Sciences.

Material and Methods

In a cross-sectional retrospective analysis study, we reviewed the files of 60 APL patients. Forty two cases had a complete flowcytometric analysis (acute leukaemia panel of our center).
Flowcytometry was done from bone marrow aspirates by the FACS caliber, Becton Dickenson apparatus. Number of white blood cells, platelets, and haemoglobin levels have been recorded from the patient’s blood on the day of their admission, by using H1(Bayer) automated cell counter . The cell morphology and percent of Bone marrow Promyelocytes (Blasts) were obtained from the patient’s bone marrow aspiration cytological reports. Other demographic and immunophenotyping information, as well as CD34 expression, got special attention.

For the evaluation of DFS, the time between complete remission till relapse, or the last follow up that showed complete remission status or death from unrelated causes, was an important criterion. The role of age, sex, WBC, platelet, count, haemoglobin rate, percent of marrow blasts, purpura, and CD34 expression in remission-induction (CR) and DFS were analyzed. The relationship between CD34 expression and the same factors were also evaluated. Any percentage expression of CD34 was recognized as positive in our cases.
According to age and WBC count, the patients were divided into group A (more or less than 30 years), group B (more or less than 60 years), and WBC more or less than 10000/ μl, respectively (2).

Regarding platelet count, patients were divided into those with less or more than 20000/μl. A Haemoglobin level of 10 gr/dl was also considered as analytical range (threshold). Datas were analyzed statistically by SPSS13 software after extraction from patient’s files, and Khey 2 and T tests were used for statistical analyzing the datas correlated with CR and DFS.

Since 11 of 60 cases died before starting treatment, they were not considered for evaluation of the above mentioned factors with CR .We analyzed this part of the study only for 49 patients, and because only 28 cases had reached CR and DFS, the correlation between the mentioned factors in the checklist was evaluated for 28 patients, and p<0.05 was considered significant.

Results

Of 60 patients evaluated, 34 (56.7%) were males and 26 (43.3%) were females. Cases were in the range of 11-71- year- old, and mean age was at 33.63.The highest age related to incidence, was 30-39 years. (Table/Fig 1) shows the characteristics of the studied cases. Of 39 patients that were checked for CD34, 2 cases (5.1%) were considered positive regarding 20% severity counting as cut off point, and 4 cases (10.3%) were considered positive without considering any cut off point (Table/Fig 2). Only one out of 4 CD34+ patients had hypogranular morphology, and from 49 cases treated, 28 patients (57.1%) entered remission, and 11 patients who had died before starting treatment were not considered in the statistical analysis.

(Table/Fig 3) shows the survival range of 28 patients' conjunctions with CR rate.DFS was estimated least and last 1 and 63 months respectively. As a mean they had 18.76 months DFS.
Of 28 cases who entered CR, 16 were males and 12 females (P=0.777).Mean DFS was 16.42 ± 4 months (P=0.495). All of the cases with CR were under 60-year-old (P=0.179), and the mean DFS was 18.76 ± 2.9 months (Table/Fig 4).Nineteen patients with CR (67.9%) had purpura or overt bleeding at presentation (P=0.553), and their mean DFS was 16.84 ± 2.8 months (P=0.347).Of 19 CR patients, 3.6% had marrow blast count less than 70%, and the rest (92.4%) had marrow blast count equal or more than 70%(P=1.000) and the mean DFS was 19.39 ± 2.9 months (P=0.276).None of the 28 cases that entered CR showed CD34 expression, and of those 21 cases that did not enter CR , 3 cases (18.8%) expressed CD34 positivity (P=0.086).

One of the CD34+ cases died before starting of treatment, and so we omitted it from the statistical analysis in this part of the study. The mean DFS of CD34 negative patients was 16.15± 3.05 months.
Twenty seven out of 28 patients who entered CR, had hypergranular morphology (P=1.000), and the mean DFS was 20.53±4.3 months. Regarding the only case in CR with hypogranular morphology, who had DFS of 7 months, there was no significant statistical difference (P=0.448).

Results of CD34 positivity in relationship with cell morphology and other factors:Because CD34 expression was checked only in 39 cases, we considered only these 39 cases for statistical analysis in this part (Table/Fig 5). Three out of 4 CD34+ (10.25%) were hypergranular (P=0.197).


Discussion

Many biological and clinical factors are involved in the prognosis of APL patients, from the point of remission induction and relapse rate. It is believed that gender plays a prognostic role, and that the prognosis is poor in males(2).Twenty eight out of 49 treated patients entered complete remission in our study. Sixteen of these (57.1%) were males. This is the similar to the results of a study of 47 cases with female dominancy, but without any significant statistical differences (2). Older age (>60 years) plays a negative role in prognosis of AML patients (12). All the patients who had entered CR were less than 60 years old in this study.

It is thought that a platelet count of less than 40,000/μl at presentation is a favorable prognostic factor with respect to relapse (14). Twenty out of 28 patients who entered CR (71.4%) in our study had a platelet count of more than 20,000/μl, that was not significant from statistical point of view. The same results were obtained from a study which was trying to show the correlation between CD34 positivity and CR and platelet level in APL patients (2) . DFS was also low in patients with platelet counts less than 20,000/μl but statistical analysis did not show any significant difference between cases with higher and lower than 20,000/μl platelet counts and DFS. Some studies stressed that lower platelet count at diagnosis is related to early and consequent lower DFS (2) .
In spite of some studies we could not show any significant correlation between WBCs and CR. Meanwhile, there was no correlation between appearing purpura and CR in our patients, but in a study with 196 APL patients, the absence of purpura or fine purpura was considered as a favorable factor in the development of CR (P=0.461), (13).

In most studies, expression of CD34 on the surface of APL cells was considered as a poor prognostic factor(15),but there are also some studies that could not addressed it (15),(16). However, there were no statistically significant differences in the other clinical parameters, such as age, haemoglobin level, WBC , platelet count between the CD34+ and CD34- groups in the Albano et al study. On the other hand, they didn’t find any differences between the two groups in terms of complete remission, overall survival, and disease-free survival (10).

Expression of CD34 on APL cells also has been considered as a poor clinical prognostic factor (2) .There are also some data reporting the poor prognostic correlation of CD34 positivity with leukocytosis and other concomitant poor prognostic clinical factors (17). Another study showed that the high WBC count (>10,000) at presentation is related to overall survival (17). .In our study, 4 out of 39 cases(10.3%) expressed CD34 on their promyelocytes, but one of which died before starting treatment. None of the 28 patients who entered CR expressed CD34.These findings indirectly show the poor prognosis related to the CD34 expression on APL cells. Still it is believed that expression of CD34 in APL may be associated with poor prognosis because of its correlation to higher WBC counts (14). In this study, CD34+ patients had lower WBC counts which differed from the results of other studies (2,10,14) . On the other hand, cases with WBC<10,000/μl showed longer DFS.

The age group less than 30 is normally considered as a favorable factor (13).The results of a study on 196 APL patients showed longer DFS in patients younger than 30 years (P=0.0003),but in our study, the patient’s lowe

Conclusion

Poor correlation in most prognostic parameters in this study, may be because of shortage of sample size ,but it could be related to a different natural history of APL in our district or as an effect of race or other ecological factors.

References

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ZHU Hong-hu , LIU Yan-rong , QIN Ya-zhen , JIANG Bin , SHAN Fu-xian , WU Shu-lan et al (2007). Detecting PML-RARα transcript in acute promyelocytic leukemia using real-time quantitative RT-PCR. Chinese Medical Journal,120 (20):1803-1808.
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Lee JJ, Cho D, Chung IJ, Cho SH, Park KS, Park MR, Ryang DW, Kim HJ (2003). CD34 expression is associated with poor clinical outcome in patients with acute promyelocytic leukemia. Am J Hematol, 73(3), 149-53.
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Ventura GJ, Hester JP, Dixen Do, Khorana S, Keating MJ (1989). Analysis of risk factors for fatal hemorrhage during induction therapy of patients with acute promyelocytic leukemia. Hamatol pathol, 3(1), 23-8.
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Zhao W, Wang X, Guo W, Qu B, Wang H, Shen Z et al(2000). Hemostatic abnormalities associated with acute promyelocytic leukemia and corrective effects of all-trans-retinoic acid or arsenic trioxide treatment. Chin Med J(Engl), 113(3), 236-40.
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Kaleem Z, Crawford E, Pathan MH, Jasper L, Covinsly MA, Johnson LR, et al(2002). Flow cytometric analysis of acute leukemia’s Archives of pathology and laboratory. Arch Pathol Lab Med, 127(1), 42-48.
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Tallman MS, Nabhan C, Feusner JH, Rowe JM (2002). Acute Promyelocytic leukemia: Evolving therapeutic strategies, Blood , 99(3), 759-767
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Jurcic JG, Soignet SL, Maslak AP (2007). Diagnosis and treatment of acute promyelocytic leukemia. Curr Oncol Rep, 9(5) :337-44.
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Albano F, Mestice A, Pannunizo A, Lanza F, Martino B, Pastore D,et al (2006).The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34- CD2- Hypergranular (M3) and microgranular (M3v) phenotypes. Haematologica /the hematology journal , 91(3):311-316.
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Tables and Figures
[Table / Fig - 1] [Table / Fig - 2] [Table / Fig - 3] [Table / Fig - 4] [Table / Fig - 5]

JCDR is now Monthly and more widely Indexed .