Leukemia Research Vol. 16, No. 10, pp. 1055-1056, 1992. Printed in Great Britain.

0145-2126/92 $5.00 + .00 © 1992 Pergamon Press Ltd

L E T T E R TO THE EDITORS

SUCCESSFUL T R E A T M E N T OF TWO CASES OF MYELODYSPLASTIC SYNDROME COEXISTENT WITH CHRONIC LYMPHOCYTIC L E U K A E M I A WITH LYMPHOBLASTOID I N T E R F E R O N

THE coexistence of myelodysplastic syndromes (MDS) and chronic lymphocytic leukaemia (CLL) in untreated patients seems to be rare. Copplestone et al. [1] identified only 3 cases with coexistent previously untreated CLL in a series of 190 myelodysplastic patients. Recently, Vallespi et al. [2] reported 3 similar cases in their large series of patients with MDSs. Bone marrow (BM) lymphoid aggregates are a frequent occasional finding in the elderly and immunological abnormalities [3] with reactive increase of BM lymphocytes are not infrequent in MDSs. Thus, the diagnosis of MDS with concurrent CLL must be carefully verified. In addition, the physiopathologic basis for this mixed disorder remains poorly understood. Different therapeutic approaches have been attempted in cases that required cytostatic treatment: mini-CHOP [4], CVP [5], chlorambucil (CLB). A good control of lymphocytosis has generally been reported, but with a disappointing haematologic toxicity. We present here two cases of hybrid disorder MDS/CLL successfully treated for a long period with lymphoblastoid interferon (Iy-IFN) without any significant toxicity. Case 1--an 81-year-old woman, referred in June 1989 (Fig. 1A) was firstly diagnosed of refractory anaemia (RA) (Hb 8.9g/dl, MCV l14u 3, WBC 8.5 × 103/dl with a differential count of N.10%, M.2%, L.88%, Pits 145 × 103/dl). BM aspirate: hypercellular, with marked dyserythropoiesis and dysgranulopoiesis. BM histology: hypercellular myelodysplasia; some lymphoid aggregates. The immunophenotyping (IP) of PB showed that 92% of lymphocytes were positive for CD19, 5, 20, 22, slg(DIM) and r light chains. Prednisone (PDN) (50 mg/d) was started. Five months later the patient's lymphocytes were 19.2 x 103/dl and showed the same typical CLL IP-pattern. A BM aspirate showed 40% lymphocytes together with dysplasia. A diagnosis was made of B-CLL associated with RA. The patient received 4 courses of CLB (10 mg/d × 7 dd) and PDN (50mg/d × 7dd). WBC count fell to

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FIG. 1. Clinical course of case 1 (A) and case 2 (B).

2.9 x 103/dl, but transfusion requirements greatly increased and thrombocytopenia insurged. Chemotherapy was therefore discontinued and, 2 weeks later, ly-IFN (Wellferone, Wellcome Ltd, London) was administered (3MU 3 times/week s.c.). After 1055

1056

Letter to the Editors

two months of t r e a t m e n t , transfusions were discontinued and cytopenias greatly improved; after six months only a maintenance regimen ( 2 M U / w e e k s.c.) was required and, at present, a very good clinical picture has been achieved. Case 2 - - a 72-year-old w o m a n presented in August 1990 with PB cytopenias ( H b 9.2 g/dl, M C V 108.4 u 3, W B C 3.8 × 103/dl with a differential of N . 6 6 % , M . 6 % , L.28%, Plts 20 × 103/dl) (Fig. 1B). BM histology evidenced a R A R S picture with A L I P and lymphoid aggregates. Danazol therapy was ineffective and in J a n u a r y 1991 the IP of PB-lymphocytes showed a 97% positivity for CD19, 22, 5, 25, sIg(DIM) and K chains. A steroid therapy was undertaken. Subsequently, transfusions could be avoided and t h r o m b o c y t o p e n i a improved, but lymphocyte n u m b e r raised (8.9 × 103/dl). BM showed 20% lymphocytes and trilineage dysplasia. Ly-IFN was started (3 M U 3 t i m e s / w e e k s.c.). T h r e e months later H b was 11.6g/dl, lymphocytes 3.2 × 103/dl and Pits 118 x 103/dl. A maintenance schedule was begun obtaining, at the date, a further haematologic improvement. On the basis of our observations we propose low doses of IFN as a safe and effective first-line therapeutic approach for cases of hybrid CLL/low-risk MDS. REFERENCES 1. Copplestone J. A., Mufti G. J., Hamblin T. J. & Oscier

D. G. (1986) Immunological abnormalities in myelodysplastic syndromes. II. Coexistent lymphoid or plasma cell neoplasms: a report of 20 cases unrelated to chemotherapy. Br. J. Haemat. 63, 148-159. 2. Vallespi T., Torrabadella M., Ruiz-Marcellhn C., Irriguible D., Jaen A. & Sans M. (1991) Myelodysplastic syndrome associated with chronic lymphocytic leukaemia: a report of three cases. Leukemia Res. 15 (Suppl,), 20. 3. Gebbia V., Miserendino V., Colucci A., TamboneReyes M., Rausa L., Di Marco P. & Citarrella P. (1989) Analysis of human dysplastic haematopoiesis in long term bone marrow culture. Blut 59, 442448. 4. Bastion Y., Thomas X., Felman P., Campos L., Charrin C. & Coiffier B. (1991) High risk myelodysplastic syndrome coexistent with chronic lymphocytic leukemia for more than 9 years: inhibition of the myeloid clone by the lymphoid clone? Leukemia 5, 1006-1009. 5. Bracey A. W., Maddox A. M., Immken L., Hsu S. M. & Marks M. E. (1989) Coexistence of myelodysplastic syndrome and untreated chronic lymphocytic leukemia with development of acute myeloid leukemia immediately after treatment of chronic lymphocytic leukemia. Am . J. Hemat. 30, 174-180. M. TAMBONE-REYES P. Dl MARCO D. TINN1RELLO S. GRISANTI

P. C1TARRELLA

Chair of Hematology I Institute of Internal Medicine University of Palermo Italy