Sanger, R. (1982) Pathogenetic signlficance of ‘pure’ monosomy 7 in myeloproliferative disorders. Analyses of 14 cases. Human Genetics. 62, 40-5 1.

Pedersen-Bjergaard, J., Philip, P., Mortensen, T.B., Ersboll, I., Panduro. J., Jensen, G . & Thomsen, M. (1981) Acute non- lymphocytic leukemia, preleukemia. and acute myeloproliferative syndrome secondary to treatment of other malignant disease. Clinical and cytogenetic characteristics and results of ‘in vitro’ culture of bone marrow and HLA typing. Blood, 57,4.

Second International Workshop on Chromosomes in Leukaemia (1980) Cancer Genetic and Cytogenetics. 2, 89-113.

COMPLETE REMISSION IN PLASMA CELL LEUKAEMIA

In a recent issue of British Journal of Haematologg, Monte- cucco et al (1986) reported the achievement of a complete remission in two cases of plasma cell leukaemia (PCL). This led them to suggest that the clinical course and response to treatment of PCL might be quite different from that in multiple myeloma (MM) and more like that seen in acute leukaemia. To support this suggestion we would like to report a case of PCL in which a complete remission was obtained after combination chemotherapy, only to relapse later in a rather unusual fashion.

A SO-year-old nurse presented with a 6-month history of asthenia and back pain but no abnormal physical findings. A bone marrow aspirate showed a 90% immature plasma cells with 1.21 x 109/1 present in the peripheral blood. No para- protein was found in serum and 3.2 1 g of kappa light chains were daily excreted in her urine. Hypercalcaemia and a creatinine of 45 pnol/l were also found. X-ray examination showed small lytic lesions in the pelvis, left femur and both scapulae. A diagnosis of PCL was made and treatment was begun with the M-2 protocol (Case et al, 1977). After four courses (20 weeks) she was found to be in complete remission with no plasma cells in her blood or marrow and no paraprotein in the urine. Calcium and creatinine levels were also normal. Previous lytic lesions persisted but no new ones had appeared. A fifth course was given but 32 weeks after diagnosis she presented with a right orbital mass whose biopsy showed atypical plasma cells. Although a sixth course of M-2 was given and later a VAD combination (Barlogie et al, 1984) the size of the orbital mass increased and new masses appeared subcutaneously on her back. Bone marrow remained in remission but paraprotein reappeared in urine.

a-INTERFERON IN MYELODYSPLASIA

Correspondence 145 Swolin, B., Weinfeld, A., Westin, J., Waldenstrom, J. & Magnusson, B.

(1985) Karyotypic evolution in Ph-positive chronic myeloid leukaemia in relation to management and disease progression. Cancer Genetic and Cytogenetics. 18, 65-79.

Yunis. J.J.. Brunnlng, R.D.. Howe. R.B. & Lobell. M. (1984) High- resolution chromosomes as an independent prognostic indicator in adult acute non-lymphocytic leukemia. New England Journal of Medicine, 311, 812-817.

She died 50 weeks from diagnosis after a stormy clinical course.

As shown by this case, the pattern of evolution followed by PCL and MM seems to be very different, PCL resembling that seen in high grade lymphomas or acute leukaemias with a rapid clinical course and a higher sensitivity to chemo- therapy. On the contrary MM usually presents a more indolent course with leukaemic pictures being unusual even in a terminal situation (Woodruff et al, 1978). Thus PCL might represent among gammopathies the counterpart of high-grade lymphomas among non-Hodgkin’s lymphomas. These facts stress the convenience of an aggressive initial and maintenance chemotherapy for PCL.

Servicio de Hematologfa, I. KRSNIK Hospital Clinic0 de Sun Carlos, Madrid, Spain E. DEL P m o

M. A. PERALVER

J. DIAZ-MEDIAVILLA

REFERENCES

Barlogie, B.. Smith, L. & Alexanian. R. (1984) Effective treatment of advanced multiple myeloma refractory to alkylathg agents. New EnglandIournal of Medicine, 21, 1353-1362.

Case, D.C.. Burton, J.L.. III & Clarkson, B.D. ( 19 77) Improved survival times in multiple myeloma treated with Melphalan, Prednisone, Cyclophophamide, Vhcristine and BCNU: the M-2 protocol. American Journal of Medicine, 63, 897-903.

Montecucco. C., Riccardi. A.. Merl i . G. & Ascari. E. (1986) Complete remission in plasma cell leukaemia. British Journal of Haematologu, 62, 525-527.

Woodruff, R.K., Malpas, J.S., Paxton, A.M. & Lister, T.A. (1978) Plasma cell leukemla (PCL). Blood. 52,839-845.

Personal clinical observation that patients with myelodyspla- Against this background we treated a MDS patient with aIFN sia (MDS) have temporary haematological improvement with remarkable beneRt. following infective episodes suggested the possibility that a- This 69-year4d man presented with symptoms of anae- interferon (aIFN) played some role in myelopoiesis. Further- mia. A full blood count revealed haemoglobin 6.4 g/dl (MCV more. endogenous aIFN production in MDS is reduced as part 11 6 fl), white cell count (W) 1.9 x 109/1 (0.6 x lO9/l of depressed lymphocyte function (Okabe et ul. 1986). grandocytes with 0.16 x 109/1 myeloblasts), platelets

146 Correspondence Table 1.

Before After Normal (n = 2 5) IFN therapy JFN therapy

PB neutrophil phenotype My9 (CD33) 11.4f 2.4% 28.8% 15.3% Mol (CDl1) 84*6f2*9% 32.6% 65.1% Leu 15 (CDl1) > 90% 60.2% 67.3%

NK cells (Leu Ila+) % PBM 16.7 f 2% 26% 38% Absolute count 0*5f0*1 x 109/1 0.37~ 1O9/I 0.45 x lo9/]

NK activity at various effector:target ratios 50: 1 46.6f6.2% 12.9% 34% 25:l 40.3 f 6.3% 9% 24.7% 15:l 32.5f 5.2% 6.2% 18.2% 10: 1 24f4.0% 5% 10.3% 5:l 15.3f2% 4.8% 6.6%

11 6 x 109/1. Serum B12 and folate were normal. Bone marrow revealed dyserythropoiesis (but no ring sideroblasts) and dysmyelopoiesis with Pelger-Huet cells and the following myelogram: neutrophils 18%, lymphocytes 7%, nucleated red cells 35%, monocytes 2%, myelocytes 5%. metarnyelo- cytes 2%, plasma cells 2%. promyelocytes 1%. blasts 18%. A diagnosis of refractory anaemia with an excess of blasts (RAEE3) was made, with the poor prognostic features (anae- mia, neutropenia, thrombocytopenia. excess blasts) defined by Mufti et al(1985). The patient was transfused with 5 units of blood and commenced on 3 megaunits of a-IFN (Wellferon) subcutaneously each day.

Following an initial fall in neutrophil count this rose to 2-2 x 109/1 by 6 weeks and 4.6 x 10y/l by 4 months therapy. His haemoglobin followed a similar pattern stabilizing at around 12 g/dl. Platelets remain around the 80 x 109/1 mark. Bone marrow examination at 6 weeks revealed less dyseryth- ropoiesis, and myelopoiesis was improved (neutrophils 4 1 %, lymphocytes lo%, nucleated red cells 17%, monocytes 5%, myelocytes lo%, metamyelocytes 8%, plasma cells 4%, promyelocytes 2%. basophils 0%. blasts 2%).

Indirect immunofluorescence revealed increased periph- eral blood (PB) neutrophil maturity (Baumann et al. 1986) and natural killer (NK) cells following 12 weeks Wellferon therapy (see Table I). NK function, as determined by a standard 51chromium release assay, was also improved after Wellferon therapy.

The initial side effects of Wellferon were well tolerated and resolved quickly.

Universitu Department of Haematology, Duncan Building. Roual Liverpool Hospital. Prescot Street. PO Box 147, Liverpool L69 3BX

Wellcome Research Laboratories, Lungleu Court. Beckenham, Kent

D. W. GALVANI J. C. CAWLEY

A. NETHERSELL J. M. BOTTOMLEY

REFERENCES

Baumann, M.A., Keller, R., McFadden, P.W., Libnock, J. & Patrick, C.W. (1986) Myeloid cell surface phenotype in myelodysplastic states: evidence of an early diEferentiation antigen. American j o u m l ojHernuto1ogM. 22,251-257.

Mufti. G.J., Stevens, J.R.. Oscier, D.G., Hamblln. T.J. & Machin, D. (1 98 5) Myelodysplastic states - a scoring system with prognostic significance. British j o u m l ofHaernatolog#. 59,425433.

Okabe, K.. Minagawa, T.. Nakane. A., Sakurada, K. & M i y d i . T. (1986) Impaired ainterferon production and natural killer activity in blood mononuclear cells in myelodysplastic syndromes. Scandf- navfan journal oj Huernatologll, 37. 1 11-1 17.

BAYESIAN ANALYSIS OF DNA HAPLOTYPE ASSOCIATIONS IN p THALASSAEMIA AND APPLICATIONS TO PRENATAL DIAGNOSIS

The article by Wainscoat et a1 (1 986) on prenatal diagnosis of /3 thalassaemia demonstrates again how genetic linkage can be applied to prenatal or presymptomatic diagnosis of diseases. DNA polymorphisms occur at various restriction enzyme sites in the B globin gene cluster (Kan 81 Dozy, 19781,

and together these identieable polymorphisms form a marker haplotype. Once a particular marker haplotype is found to be Linked to a thalassaemic allele in a family, the marker haplotype can be used to prenatally identify thalassaemic alleles transmitted within that family. The article also