IMMUNOPHENOTYPIC PROFILE OF T ACUTE LYMPHOBLASTIC LEUKAEMIA IN A TERTIARY CARE CENTRE-OUR EXPERIENCE

Dr. Sumayya Shah and Dr. Saleem Hussain Mir Senior Resident, Department of Hematopathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 20 September 2020 Final Accepted: 24 October 2020 Published: November 2020


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have T-ALL due to the presence of various T cell markers with absence of B/Myeloid markers. There are no previous papers in the literature that have studied the characteristics of T-ALL in Kashmiri patients. Hence, the full picture of the disease development and outcome in this group is not completely understood. We sought to study and classify the immunophenotype characteristics of Kashmiri patients diagnosed with T-ALL and to correlate the results with age and gender as well as biological factors (peripheral total leukocyte counts and bone marrow blast percentage) to understand the characteristics of the disease in Kashmiri patients. This will guide us to better predict disease outcome and decide a suitable plan of treatment.

Materials And Methods:-
All T-ALL patients were included in this study who had registered in our hospital from October 2015 to September 2020. These totalled 36 cases. All relevant data pertaining to these patients was obtained from the hospital information system database. Informed consent was taken from the patients or their guardians as well as approval from the ethics board of our hospital. Patients with missing data regarding diagnosis or insufficient sample for obtaining results were excluded from the study.

Results:-
Out of 36 total cases, 7 were female. However, one female was a case of T-ALL turned Therapy related AML and her previous records of T-ALL diagnosis were unavailable. Hence, she was excluded from the study.
Of the remaining 6 females, 4 (11.43%) were diagnosed with pro T-ALL phenotype, 1 (2.86%) with common thymocyte T-ALL and 1 (2.86%) was diagnosed with mature thymocyte T-ALL phenotype. Of the 4 cases with pro T ALL, 1 was diagnosed as ETPALL (Early T cell Precursor Acute Lymphoblastic Leukaemia) ( Table 1).
Overall, 10 cases (28.57%) were of pro T-ALL phenotype, 18 (51.43%) were of common thymocyte phenotype and 7 (20%) were of mature thymocyte phenotype (Table 1). The average age of patients with pro, common thymocyte and mature thymocyte T-ALL was 31.4, 12.8 and 14.67 years (6 of 7 cases of mature thymocyte T-ALL as age of one patient was not mentioned in records), respectively. Among female patients, the average age at presentation was 21.83 years and among males, it was 17.3 years. The average age of T-ALL cases as a whole (34 of 35) was 18.60 years.

T-ALL subsets
CD1a was positive in 18 cases of common thymocyte T-ALL (as per definition) (51.43%) and negative in remaining 17 (48.57%) cases of pro and mature thymocyte T-ALL (Fig 1).

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CD2 was run in all cases except 11. In the remaining 24 cases, CD2 was positive in 17 (70.83%) and negative in 7 (29.16%). Among the 17 positive cases, 7 cases were of pro T-ALL, 8 were of common thymocyte T-ALL and 2 were of mature thymocyte T-ALL.
CD3, being a lineage marker specific for T cells, was positive in all cases. Cytoplasmic CD3 was not run in 13 cases while surface CD3 was not run in one case. All 13 cases (37.14%) showed surface positivity, 19 cases (54.29%) showed cytoplasmic positivity and 3 cases (8.57%) showed both surface and cytoplasmic positivity.
CD5 was positive in all cases (88.57%) except 4 (11.43%). 17 cases were of common thymocyte T-ALL and 7 cases each were of pro and mature thymocyte T-ALL (Fig 1).
CD7 was positive in every case.

Discussion:-
T-ALL is a relatively rare disease and paucity of cases as well as incomplete data documentation at our institution made it even harder to correctly assess this disease in our population. However, using 3 main markers i.e. CD3 (surface and cytoplasmic), CD1a and CD7, we were able to study the immunophenotypic characteristics of this disease according to the WHO classification [5]. The WHO classification segregates T-ALL into three types based on the presence or absence of CD3, CD1a and CD7 i.e., pro T (cCD3+,CD1a-, CD7+, sCD3-), commonthymocyte 955 T-ALL (cCD3+, CD7+, CD1a+) and the mature thymocyte T-ALL (cCD3+, CD1a-, CD7+, sCD3+).CD3 is a lineage determining marker and is therefore positive in all cases.
A study by Pullen et al determined that several of the clinical and laboratory prognostic factors, which are used reliably for B-ALL, are much less predictive in T-ALL (age, TLC, consensus risk group, etc.) [10].
We found that T-ALL is more common among males (82.86%) than females (17.14%) with a male-to-female ratio of 4.83:1, with common thymocyte T-ALL more common (51.43%) than pro and mature thymocyte T-ALL (28.57% and 20% respectively). Our study was at variance with another study which found pre T-ALL cases to be much fewer (4.2%) than T-ALL cases (26.4%) [3].
Of importance is the fact that of the 6 female cases, 4 cases (14.28%) were found to have pro T-ALL including one case of ETPALL and 1 patient each (2.86%) was found to have common and mature thymocyte T-ALL.
The importance of studying the immunophenotypic markers of T-ALL in a given population is their prognostic significance for determining various parameters such as remission rate, event free survival, overall survival, risk of relapse etc.
CD1a was positive in a little more than half of all cases (51.43%). A study in Moroccan children by Lahjouji et al found an excess of the common thymocyte subtype (80.4%) displaying reactivity with CD1a as compared with the frequency reported by others [8].
Among the cases in which CD2 was run, it was found to be positive in 70.83% patients. A study by Uckun et al found a statistically significant correlation between the CD2 antigen positive leukemic cell content of bone marrow and probability of remaining in bone marrow remission, as well as overall event-free survival (EFS) [12].
Cytoplasmic CD3 is a lineage specific marker for T cells. 51.43% cases were positive while 40% showed surface positivity and 8.57% showed both surface and cytoplasmic positivity. CD5, along with CD2 and CD7 is a marker for immature T cells. Majority of the cases (88.57%) were positive. All cases were positive for CD7.
CD34 is a marker for haematopoietic stem cells and was positive in only 34.3% cases. This is in agreement with a study by Pui et al and a couple of other studies which have found expression of this antigen rare/absent by malignant T lymphoblasts [9].

Conclusion:-
This study is the first to report the different immunophenotypes of T-ALL in Kashmir in the English language literature. It is hoped that this study serves as a starting point for further, more detailed studies on this disease in our population eventually leading to better tailored treatment regimens that fit our population characteristics.