January 1985, Volume 35, Issue 1

Original Article

Acid Phosphatase Positive T-Lymphoblastic Leukaemia (T-ALL) ifl Pakistani Children

Mirza Naqi Zafar  ( Zafar Research and Diagnostic Centre ,7/14 Rimpa Plaza, M.A. Jinnah Road, Karachi. )
S.H.M. Zaidi  ( Dept. of Radiotherapy, Jinnah Postgraduate Medical Centre, Karachi. )

T-Lymphoblastic leukaemia (T-ALL) appears to be associated with factors known to be of bad prognosis in Acute lymphocytic leukaemia (ALL). Acid phosphatase reaction (AP), a specific non-immuno­logical cytochemical marker for T-ALL was performed on peripheral blood and bone marrow slides of fifty children with ALL to assess the frequency of T-ALL in our population. Myeloperoxidase (P) and Alpha-Napthyl Esterase (NASA) were performed to exclude Acute myelocytic and Monoblastic leukaemia. A strong localised AP reaction in more than fifty percent of the blasts was taken as positive for T-ALL. Of the fifty cases studied 32% showed strong AP positivity in majority of the cells. These were negative for both P and NASA and showed varied Periodic Acid Schiff (P.A.S) positivity. This high frequency of T-ALL in our series may explain the poor response to therapy and high relapse rates observed in our population. (JPMA 35: 6, 1985).

Introduction

There are several techniques to demonstrate Acid phosphatase (AP) activity in blood and bone marrow films1,2. The ‘AP reaction in Acute leukaemia is of most value in Apute lymphocytic leukaemia (ALL) where several workers3,4,5,6,7 have demonstrated a characteristic strong localised reaction in T-lymphoblastic leukaemia (T-ALL). In a comparative study8 90% of the cases of T-ALL were strongly positive for AP in contrast to 2% in common-ALL and 10% in Null-ALL. These Null cells however may in fact be prelymphoid stem cells or many be cells of T-lineage which have an incomplete T-phenotype. In another study9  of 9 cases of T-ALL which expressed the T antigen (but were Sheep rossette negative )7 showed a strong paranuclear AP reaction, thus implying that this reaction may be of value in the characterisation of T-lymphoblasts when sheep red blood cells rossettes are negative.
T-ALL in general appears to be associated with factors known to be of bad prognosis in ALL. Meningeal leukaemia presumably related to initial high white cell count is commonly an early event.10 ‘Splenomegaly is a more constant feature in T-ALL than Null-ALL11. The remission rate to conventional ALL therapy has been reported to be 40% in T-ALL as compared to 89% in other ALL cases12. Comparision of groups of similar white cell counts and organomegaly, similar drug schedules resulted in earlier relapses and shorter survival in T-ALL, thus suggesting an intrinsically more malignant nature of the T-cell neoplasia12  Relapse rates of 45% in T-ALL as compared to 15% in Null-ALL have been repprted13
This study was conducted to evaluate the frequency of T-ALL in our population employing AP reaction as a positive cytochemical marker for 1-ALL. Myeloperoxidase (P) and Alpha-napthyl esterase (NASA) were employeth to exclude, Acute myelocytic and monocytic leukaemias while Periodic acid Schiff (P.A.S) reaction was employed as a positive markers for other ALL.

Material and Methods

Pretreatment samples of bone marrow and or blood from fifty cases of ALL were collected from various hospitals in Karachi. Slides were used for AP reaction by the method of’. Romanosky stained films were looked at in all cases. P and NASA were performed14,15 to exclude acute myeloid and monocytic leukaemia and P.A.S stain was performed by the method of16 ALL cytochemical reactions were performed using Sigma Kits. Cases were scored as AP positive when more than 50% of the blasts showed a characteristic strong reaction usually localised to the area of the cytoplasm corresponding to the Golgi apparatus.

Results

Of the fifty children with ALL which were included in this series, sixteen showed strong localised AP activity in more than 50% of the blasts (Fig. 1 and 2).


All these cases were negative for P (Fig. 3)

and reduced activity was observed in NASA and P.A.S (Fig. 4).


Table shows activity in % of blasts of AP, P, NASA and P.A.S.

Discussion

Acid phosphatase reaction was employed in this study as a positive non-immunological cytochemical marker for T-ALL. Since AP is also positive in some cases of acute myelocytic and monocytic leukaemia, myeloperoxidase and Alpha-napthyl esterase were performed and found to be negative or low in all cases positive for AP. Our experience was similar to others3  where low P.A.S positivity was found in AP positive 1-ALL. In fact within the ALL,P.A.S is mostly positive in Non-T and Null-ALL3.
This study reports a 32% frequency of T-ALL in Pakistani children with ALL as compared to Western reports where frequencies of 15-20% have been reported17. This study suggests firstly a continental variation in types of ALL since T-ALL is a rare disorder in Western countries and secondly that this high frequency of T-ALL in our children may explain the observed low remissions and high relapse rates in Pakistani children.

Acknowledgement

This project was funded by the Pakistan Medical Research Council. We are grateful to Dr Ejaz Vohra and Dr. Malick of Dr. Ziauddin Hospital, Prof.Mushtaq Ahmed and Dr. M.A.Arif of Paediatric Dept, NICH, and Dr Ghaffar Billo and Dr D.S.Akram Paediatric Dept. Dow Medical College for providing material and patients to make this study possible.

References

1. Goldberg, A.F. and Barka, T. Acid phosphatase activity in human blood cells. Nature, 1962; 195: 297.
2. Perase, A.G.E. Histochemistry; theoretical and applied. 3rd ed. London, Churchill, 196?.
3. Catovsky, D., Galetto, J., Okos, A., Milliani, E. and Galton, D.A.G. Cytochemical profile of B and T leukaemic lymphocytes with special reference to acute lymphoblastic leukaemias. J. Clin. Pathol., 1914; 27:767.
4. Ritter, J., Gaediske, G., Winkler, K., Beckmann, H. and Landbeck, G. Possible T-cell origin of lymphoblasts in acid phosphatase-positive acute lymphatic leukaemia. Lancet, 1975; 2:75.
5. Catovsky, D., Frish, B. and Van Noorden, S. B,T and Null cell leukaemias; electron cytochemistry and surface morphology. Blood Cells, 1975, 1:115.
6. Stein, H., Petersen, N.,Gaedicke, G., Lennert, K and Landbeck, G. Lymphoblastic lymphoma of the c onvulated type-a tumor of T precursor cells. Int. J. Cancer, 1976; 17 : 292.
7. Brouet, J.C., Valensi, F., Daniel, M.T., Flandrin, G., Preued’ Homme, J.L. and Seligmann, M. Immunological classification of acute lymphoblastic leukaemias: evaluation of its clinical signi­ ficance in a hundred patients. Br. J. Haematol., 1976;33 : 319.
8. Catovsky, D., Cherchi, M., Greaves, M.F., Janossy, G., Pain, C. and Kay, H.E.M. Acid-phosphatase reaction in acute lymphoblastic leukaemia. Lancet,1978; I : 749.
9. Thiel, E., Rodt, H., Netzel, B., Huhn, D., Wondisch, G.F., Hass, R.J., Bender-Gotze, C.L. and Thierfelder, S. T-zell antigen positive, E Rosset ten negative akute lymphoblasten luekaemie. Blut., 1978; 36 : 363.
10. Wantanbe, A., Sullivan, M.P., Sutow, W.W. and Wilbur, JR. Undifferentiated lymphoma, non­ Burkitts type; menmgeal and bone marrow involvement in children. Am. J. Dis. Child., 1973; 125 :56.
11. Catousky, D. Cell markers in acute lymphoblastic leukaemia and lymphoproliferative disorders. Recent Adv. Haematology, 1977; 2:201.
12. Ravindranath, Y., Kaplan, J. and Zuelzer, W.W. Significance of mediastinal mass in acute lympho­ blastic leukaemia. Pediatrics, 1975; 55 : 889.
13. Sen, L. and Borella, L. Clinical importance of Lymphoblastic with T markers in childhood acute leukaemia. N. Engl. 3. Med., 1975; 292 : 828.
14. Kaplow, S.L. Simplified myeloperoxidase stain using benzidine dthydrochloride. Blood, 1965 26 : 215.
15. Daniel, M.T., Flandrin, G., Lejeune, I., Liso, P. and Lortholari, P. Les esterases specifiques mono­ cytaires. Utilisation dans la classification des Jeucemies aigues. Nouv. Rev. Fr. Hematol., 1971; 11: 233.
16. Hayhoe, F.J., Quaglino, D. and Doll, R. The cytology and cytochemistry of acute leukaemias. MRC, special report series n. 304, Her Majesty’s Stationery Office, London, 1964.
17. Benett, J.M., Catovsky, D., Daniel, M.T., Flandrin, G., Lymphoblastic Leukaemia; concordance among observors and clinical coorelations. Br. J. Haematol. 1981;47 :553.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: