Correspondence 2 8 5 Table I. Total transfusion requirement and haemostatic parameters of patients with immediate post-operative platelet counts below 1 2 0 x 10y/l (meanhSD)

Significance Study* Controlt level$

Patients in the subpopula- tions ( t i (percentage of 12 (11%) 33 (29%) the trial group))

Transfused bloods (units) 4.8d10.9 7.11k2.2 P<0.01 Average blood loss (ml) 5661404 8 1 3 ~ t 3 9 5 P=0.02

Before surgery Platelet count ( x 10y/l) 201 i-26 201 3Z 34 P>O.OS Thrombotest (s) 7 7 1 2 6 9 3 1 2 9 P>0,05

Immediately after surgery Platelet count ( x loy/[) 108+8 9 9 1 1 6 P > 0 , 0 5 Haemoglobin content (g/dl) 16 .63~1 .0 1 7 ~ 1 1 1 ~ 6 P>0.05 Thrombotest (s) 503Z11 61&12 P=O.O2 Plasma recalcified clotting time (s) 199i-26 2 0 0 1 4 7 P r 0 . 0 5

*Study group: two units of fresh blood, further transfusions with stored (2-5 d)

TControl group: only stored (2-5 d) blood. $Statistical evaluation using the Mann-Whitney U test. $For overall (total trial groups) results see Tables I and I1 in Wasser et a1 (1 989).

blood.

120 x 10y/l were found at comparable platelet counts (Table I). The increased transfusion requirement, therefore, cannot be the result of differences in post-transfusion platelet count reduction between the trial groups.

Rather, qualitative defects of platelets in stored blood must be responsible for the observed higher blood losses and transfusion requirements in the subpopulation of the control group. The differences in the thrombotest values between the subpopulations (Table I) suggest that a lower content of

coagulation factors in stored blood is a (co-) factor associated with the increased blood losses and transfusion requirement in the subpopulation of the control group.

Depurtnient of b ~ ~ m u n o k a e ~ ~ ~ u t o l o g y and Blood Bank, Uiiivemitg Hospitnl, Building I , E3-Q, Rijnsburgerweg 7 0, 2333 AA Leiden, The Netherlands

J. G. A. HOUBIERS M. N. J . M. W ~ s s w A. BRAND

CYCLOSPORIN A VERSUS ANTILYMPHOCYTIC GLOBULIN IN SEVERE APLASTIC ANAEMIA

Bone marrow transplantation and antilymphocytic globulin (ALG) are well-established treatments in severe aplastic anaemia (SAA), a high percentage of cures being achieved with both forms of therapy. However, the contribution of androgens to SAA treatment is controversial. Since 1984 different authors have investigated cyclosporin A (CyA) as an alternative treatment with contradictory results (Jacobs et a], 1985;Bridgesetal, 1987).ThereportofLeonardetal(1989) adds new information regarding the role of CyA in the treatment of aplastic anaemia.

The exact place of CyA in the treatment of SAA may be settled through current randomized trials (Gluckman et al, 1988; FrickhofeniSKaltwasser, 1988). We wish to report the preliminary results of such a study comparing CyA plus androgens versus ALG plus androgens in SAA.

Fourteen consecutive previously untreated patients were enrolled into this study, seven males and seven females. Their median age was 30 years (range 10-77). Eight cases were

idiopathic and six secondary to drugs. The inclusion criteria were those described by Camitta et al (1976). and the response criteria were the improvement of peripheral blood counts and lack of need for transfusions. At diagnosis, patients were randomized into two groups. One received ALG (4250 lymphocytotoxic units/5 kg/d for 6 d i.v.) and the other CyA (8 mg/kg/d orally). Provided toxicity was not apparent, the dose of CyA was adjusted to maintain total blood levels between 200 and 400 ng/ml. In both treatment groups oxymetholone (2.5 mg/kg/d) was added throughout. Response was evaluated at 2 months. The non-responders were crossed-over to the alternative treatment. Those who responded to ALG. were no longer treated, while those responding to CyA continued on the drug with dose tapering until it was withdrawn at 7 months.

The projected survival for all patients is 78% at 36 months, with a median follow-up of 3 1 months. The overall response was 57%. The initial response was identical for both

2 8 6 Correspondence treatments: 43%. In the ALG group one patient who did not respond died from infection before beginning CyA. In the CyA group one patient died of a hypertensive crisis and brain haemorrhage. before the response could be evaluated. In those patients in whom treatment was crossed-over some responses were observed: one out of three responded with CyA after failing with ALG, and one out of three improved with ALG after not responding to CyA. Finally, of the four patients who did not respond to immunosuppressive treat- ment, one died of infection, another was lost to follow-up, and two are presently alive and in remission after a bone marrow transplant in one, and after 1 year of treatment with oxymetholone in the other.

These preliminary results suggest that CyA seems as effective as ALG in SAA. In contrast with the results reported by Leonard et a1 (1989) and those previously published by Jacobs et a1 (1985). our study shows that CyA can be effective as first-line therapy in SAA. Differences in patients’ charac- teristics, dose and duration of therapy may account for some of the discrepancies reported. It is noteworthy that all our patients fulfilled the criteria for SAA and were treated for at least 2 months. Moreover, in our trial, androgens instead of corticosteroids are given concomitantly with CyA. The contribution of androgens to the efficacy of CyA deserves further study in future trials.

Postgraduate School of Haematology, ‘Farreras Valenti’, BENET NOMDEDE~J Hospital Clinic, MONTSERRAT ROVIRA University of Barcelona, EMILIO MONTSERRAT Villarroel 170, CIRIL ROZMAN 08036 Barcelona, Spain

Supported by grant 0593/89 from FISS.

PEDRO MARIN

REFERENCES

Bridges, R.. Pineo, G. & Blahey, W. (1987) Cyclosporin A for the treatment of aplastic anemia refractory to antithymocyte globulin. American Journal of Hematology, 26, 83-87.

Camitta, B.M., Thomas, E.D., Nathan, D.G.. Santos, G., Gordon- Smith, E.C., Gale, R.P., Rappeport, J.M. & Storb, R. (1976) Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood, 48, 63-70.

Frickhofen, N. & Kaltwasser, J.P. (1988) Immunosuppressive treat- ment of aplastic anemia: a prospective, randomized multicenter trial evaluating anti-lymphocyte globulin (ALG) versus ALG and cyclosporin A. Blut. 56, 191-192.

Gluckman, E., Esperous, H. & Devergie, A. (1988) Comparison of cyclosporine A (CyA) and horse antithymocyte globulin (H.ATG) for treatment of severe aplastic anemia. (Abstract). Blood, 72, (Suppl. 1). 42a.

Jacobs, P., Wood, L. & Martell, W. (1985) Cyclosporin A in the treatment of severe acute aplastic anaemia. British Journal of Haematology, 61, 267-272.

Leonard, E.M., Raefsky, E., Griffith, P., Kimball, J., Nienhuis, A.W. & Young, N.S. (1989) Cyclosporine therapy of aplastic anaemia, congenital and acquired red cell aplasia. British Journal of Haemato- logy, 72. 278-284.