Immunological phenotypic pattern of acute lymphoblastic leukaemia in Egypt

Leukemia Research Vol. 13, No. 7, pp. 519.-525,1989. Printed in Great Britain.

0145-212~89 $3.00 + .00 MaxwellPergamonMacmillanplc

I M M U N O L O G I C A L P H E N O T Y P I C P A T r E R N OF A C U T E L Y M P H O B L A S T I C L E U K A E M I A IN EGYPT* A Z Z A M . KAMEL, M A G D A M . ASSEM, ELAINE S. JAFFE,'~ IAN MAGRATH,:~ MOUSTAFA I. A B O U L ENEIN a n d DALAL S. HINDAWY

Clinical Pathology Department, National Cancer Institute, Cairo University, Egypt, and tLaboratory of Pathology and ~:Paediatric Branch, NCI, NIH, Bethesda, MD, U.S.A.

(Received 25 January 1989. Accepted 28 January 1989) AbstractmWe have performed immunophenotyping studies on 186 untreated cases of acute lymphoblastic leukemia (ALL) in an Egyptian population, using panels of monoclonal antibodies (mAb) and an avidin-biotin-immunoperoxidase detection system. Sixty-two of these cases were tested with a panel of mAb directed against the T-ceU markers CD2, CD4, CD8, B-cell markers CD20, kappa and lambda, the common ALL antigen (common ALLa) and class II HLA antigens. The remaining 124 cases were also tested with additional markers of T- and B-cell precursors, namely CD7 and CD19. The common leukocyte antigen, T200, was used to exclude nonhemopoietic neoplasms. Cases that remained unclassifiable were further tested with a wider panel of T-cell markers, including CD1, CD2, CD3 and CD5. In some cases multiple mAb directed against the same antigens were used. The relative frequencies of common ALL and B ALL were calculated from the total number of cases and were found to be 39.2% and 3.2%, respectively. The proportions of T-cell and null leukemias were calculated from the better characterized subgroup of 124 cases, and were found to be 50% and 4.8%, respectively. In our series, the age distribution of common ALL revealed a peak at 2-5 yr, but this was partially obscured in the entire series by the high proportion of T-cell cases, which had an age peak between 4 and 12 yr of age. Our results demonstrate marked differences in the phenotypic pattern of ALL in Egypt compared to Western Countries, the predominant finding being a relative excess of T-cell ALL and a paucity of common ALL cases. At present it is not clear whether this results from an increased incidence of T-cell ALL or a decreased incidence of common ALL.

Key words: Acute lymphoblastic leukemia, Immunological phenotypes of ALL.

INTRODUCTION

time period, it was proposed by R a m o t and Magrath [6, 7] that an increasing incidence of common A L L accounted for the development of the early age peak. This, in turn, suggested that the incidence of common A L L is in some way coupled to environmental factors encountered more often in more developed countries, such as those related to industrialization, or to socioeconomic status, or to both. Although the lack of an early age peak in less developed countries has been well documented, while an early age peak in U.S. Blacks has been identified only in recent years, it has never been d e a r l y demonstrated that this is due to a paucity of common A L L in less affluent populations, or that the age distribution of common A L L in such populations is the same as that in patients living in more affluent societies. We were interested in examining these issues in patients with A L L in Egypt; specifically, to determine the relative incidence of various A L L phenotypes and their age distribution. Only three studies of the distribution of A L L immunophenotypes in Egypt have been previously performed. One was

IN WESTERN C o u n t r i e s , the predominant immunophenotype of A L L is c o m m o n A L L , which accounts for 60-80% of all cases. T-cell A L L comprises only 11-20% of patients [1-5]. Recently, it was shown that c o m m o n A L L has a peak incidence in 2-5 yr olds. This provided an apparent explanation for the gradual appearance, throughout this century, of an early age peak in the age-specific incidence of childhood leukemia, and more specifically, of A L L [6]. Because this p h e n o m e n o n was coupled to a gradual increase in the incidence of acute leukemia (especially A L L ) in Western Countries during this * This work was supported by: NIF PL 480 Funds and USAID Research Agreement No. 03-091. Abbreviations: ALL, acute lymphoblastic leukemia; mAb, monodonal antibody (ies); PB, peripheral blood; CSF, cerebrospinal fluid; FAB, French, American, British; DAB, diaminobenizidine. Correspondence to: Professor Azza Kamel, Clinical Pathology, National Cancer Institute, Kasr El Aini Street, Fom EI-Khalig, Cairo, Egypt. 519

520

AZZA M. KAMELet al.

done without the aid of monoclonal antibodies [8], while the other two were too limited, both with regard to the panel of antibodies used, and with regard to the n u m b e r of patients studied [7, 9] for meaningful conclusions to be drawn. We have characterized a large n u m b e r of cases of A L L with an extensive panel of monoclonal antibodies, and have been able to confirm both the relative paucity of c o m m o n A L L in Egypt, and also its similar age distribution to that observed in the U.S.A. and Europe. MATERIALS AND METHODS Patients

The study population consisted of 131 males and 55 females with an age range of 18 months--64 yr. Sixty-five of the 186 cases were adults (aged ~>16yr), and 121 were children ( 2 0 % . The five cases with < 5 0 % positivity had a positivity of 20-30%, but all showed > 9 0 % blasts in the tested cell population. In cases classified as c o m m o n A L L , all except nine contained at least 40% positive cells with J5 mAb. The remaining nine cases showed a level of 20-30%, and as in T - A L L cases, all had > 9 0 % blasts in the tested population. The relative frequencies of the various immunological phenotypes are shown in Table 3. The relative

TABLE 3. RELATIVEINCIDENCEOF IMMUNOLOGICALPHENOTYPESOF ALL IN EGYPT Common ALL No. (%)

T ALL No. (%)

B ALL No. (%)

Null No. (%)

62* 124~

22 (35.5) 51 (41.1)

21 (33.9) 62 (50)

1 (1.6) 5 (4)

18 (29) 6 (4.8)

Total: 186

73 (39.2)

83 (44.6)

6 (3.2)

24 (12.9)

Number

* Cases phenotyped with CD2, 4, 8, 10, 20, K, )- and anticlass II. Cases phenotyped with the previous mAb+CD1, 3, 5, 7, 19 --- CD15 and CD45.

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AZZA M. KAMEL et al.

TABLE 4. DISTRIBUTION OF ALL PHENOTYPES AMONG FAB SUBROROUPS*

Group

Total No.

L1 1-.2 L3

40 78 6 124

Common ALL No. (%)

T ALL No. (%)

B ALL No. (%)

Null No.(%)

18 (45) 32 (41.0) 1 (--) 51

21 (52.5) 40(51.3) 1(--) 62

0 (0) 1 (1.3) 4 (--) 5

1 (2.5) 5 (6.4) 0 (0) 6

* Based on cases tested by the complete panel of mAb. frequencies of common A L L and B-cell phenotypes were calculated from the total number of cases tested, while those of T and null phenotypes were calculated from the 124 cases tested by the complete panel of mAb. The relative frequencies of common ALL, T, B, and null phenotypes were found to be 39.2%, 50%, 3.2% and 4.8%, respectively. As shown in Table 3, the expansion of the panel of mAb used has sharply reduced the percentage of unclassifiable or "null" cases from 29 to 4.8%. Of the 21 cases that would have been diagnosed as "null" without the additional mAbs, only six could not be assigned to any phenotype with the full mAb panel. The remaining 15 cases belonged to the T phenotype. Eleven of the 15 cases reacted with Leu9 (CD7). The other four cases reacted with other T-cell markers; one of them reacted only with Leu4 (CD3) and one reacted only with 121 (CD7). None of the 21 cases reacted with B4 (CD19). The relative frequencies of the various immunological phenotypes among the morphological FAB subgroups are shown in Table 4. There were no significant differences in the distribution of cases between the L1 and L2 FAB subgroups among the four phenotypes. Five of the six B-cell cases were morphologically classified as L3, the sixth as L2. On the other hand, of the eight L3 cases, two were common ALL and one had a T-cell phenotype. Table 5 shows the age distribution of the various phenotypes. No statistically significant difference in the relative incidences of the various immunological phenotypes was encountered between the adult and pediatric age groups.

The age distributions in each of the immunological subtypes are shown in Fig. 1 and the age distributions for common A L L and T ALL are shown in Fig. 2. Common ALL showed a sharp age peak between 2 and 5 yr, while T A L L showed a broad age peak distribution between 4 and 12 years. Five of the 83 T-ALL cases had an age of I>35 yr. The maximum ages encountered in the common ALL and T ALL groups were 64 and 56 yr respectively. Table 6 shows the sex distribution of the various phenotypes. There was no statistically significant predominance of either sex in any of the phenotypic groups. DISCUSSION The NCI in Cairo is the main center to which the majority of leukemic patients are referred from both urban and rural areas of Egypt. The relative frequencies of common ALL (39.2%) and T ALL (50%) encountered at the NCI are quite different from those reported in Western Countries. In several different series common ALL was reported to comprise 60-80% and T ALL 11-20% of cases [15]. The largest series published so far is that of Greaves [1], who studied patients from the UK, Eire and Denmark. He reported that in children common ALL accounted for 82.7% and T ALL for 11.3% while 6% of the cases were unclassifiable or "null". In adults in Greaves series 57.2% were common ALL, 12.8% were T ALL and 30% were unclassifiable or "null". The proportion of children with common ALL was much higher than in our series,

TABLE 5. DISTRIBUTION OF ALL PHENOTYPES ACCORDING TO AGE GROUPS*

Group Adults Children

Total No.

Common ALL No. (%)

T ALL No. (%)

B ALL No. (%)

Null No. (%)

45 79 124

17 (37.8) 34 (43.0) 51

23 (51.1) 39 (49.4) 62

1 (2.2) 4 (5.1) 5

4 (8.9) 2 (2.5) 6

Adults: I>16yr. Children