PROMYELOCYTIC CRISIS OF CHRONIC MYELOID LEUKAEMIA

The report of Van der Merwe et d (1986) on a case of acute promyelocytic transformation of chronic myeloid leukaemia (CML) with an isochromosome 17q i( 17q) in addition to the Phl chromosomal aberration, calls out attention to the clinical and cytogenetic features of this disease and to the underlying leukaemogenetic mechanism. As far as we know and as the recent report of Abe et al (1986) points out, detailed chromosome data of leukaemic cells in promyelocytic crisis of Phl-positive CML have been reported in only six cases so far. Only two of these six cases had the t(15:17) translocation (Berger et al. 1983: Hogge et ul, 1984) which is typical of de novo acute promyelocytic leukaemia (APL-FAB M3). The other four cases showed additional 8 or i( 1 7q) and Phl chromosomes. These superimposed chromosomal alterations are typical of myeloid blast crisis of CML. In the last 10 years we have observed three cases of acute promyelocytic transformation among 96 cases of Phl-positive CML. Two patients aged 38 and 51 years were male and one patient aged 58 was female. Blastic crisis occurred 23.20 and 71 months respectively after the diagnosis of CML had been made. The percentage of promyelocytes in the peripheral blood ranged from 38 to 60 (Table I). In the bone marrow, which was diffusely hypercellular. the percentage of promyelocytes varied from 50 to 65 while the percentage of myelocytes and metamyelocytes was low. Promyelocytes had an abnormal morphology: large with irregular nuclei, abundant cytoplasm and azurophilic granules densely packed in the cytoplasm. They stained strongly with myeloperolddase and Sudan Black B, weakly with PAS and acid phosphatase and failed to stain for alpha naphthylacetate esterase. All patients showed moderate anaemia and leucocytosis, and the platelet counts were normal or slightly low. There was no haemorrhage or disseminated intravascular coagulation. Two patients (nos, 1 and 2) showed three successive promyelocytic crises over an interval of 9 and 11 months respectively (Table I), remission having been obtained in times varying from 7 to 45 d with DAT polichemotherapy and prednisone. Patient 1 died with acute peritonitis when the third blast crisis occurred patient 2 died from sepsis of unknown aetiology when complete remission had been obtained, being still seriously pancytopenic. Patient 3, a long survivor of 85 months, underwent promyelocytic crisis very recently (December 1986) and remission was obtained in 15 d with DAT polichemotherapy. She is still in good condition with haematological features of the chronic phase of CML. The cytogenetic study, performed by standard and GTG banding techniques on bone marrow and pheripherat blood cells. in the chronic phase of the disease and whenever blast crisis occurred, showed: (1) in all three patients during the chronic phase a classic t(9:22) translocation without other chromosomal aberrations: (2) persistence of the same karyotype, without any evidence of the t( 151 7) translocation or of other chromosomal abnormalities in the blast crises of patients 1 and 3. In patient 2 only, when the third promyelocytic crisis occurred, a prevalent clone (90%). with an additional no. 10 and Phl chromosomes and without the t(15:17). appeared (Table I). In patient 3. when promyelocytic crisis occurred, the DNA was examined by Southern blot analysis with a Bgl 11-Hind III subgenomic restriction fragment of 1.2 kb, corresponding to an intron region of the bcr gene (Groffen et al, 1984). Rearrangements of the bcr region (breakpoint cluster region) were present as in classic Phl-positive CML (data not shown). Our Bndings suggest that acute promyelocytic transformation of CML is dlfferent from classic myeloid blast crisis or from APL. In fact, the c l ica l behaviour of our patients shows good responsiveness to therapy and high survival rate &er the first blast dsis. Concerning the cytogenetic data. only two cases out of the nine studied so far show the t( 15: 1 7) translocation as additional chromosomal abnormality and the karyotype either shows no variations (as in our patients) or shows additional abnormalities, typical of most common myeloid blast crisis, or unusual abnormalities as the t(3:21) translocation (Abe et al, 1986). The finding of an i( 17q) (Van der Merwe et al, 1986) does not seem to be a sure marker of promyelocytic crisis. In fact this abnormality is also found in thechronlcphaseofCML(Lawleretd, 1976: Rowley&Testa. 1982; Sadamori et ul, 1985). The heterogeneity of these data shows how the cytogenetic analysis must be supported by other types of evidence to understand the origin of this type of evolution. We would like to suggest that the promyelocytic