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Cytogenetic studies in 174 consecutive patients with preleukemic or myelodysplastic syndromes.

Routine cytogenetic studies were done in 174 consecutive patients with preleukemic or myelodysplastic syndromes (PL/MDS): 5 had the 5q - syndrome, 2 had refractory cytopenia, 43 had refractory anemia, 38 had refractory anemia with ringed sideroblasts, 69 had refractory anemia with excess blasts, 6 had refractory anemia with excess blasts in transition, and 11 had chronic myelomonocytic leukemia. Successful chromosome studies were accomplished in 167 patients (96%); 64 (37%) had a chromosomally abnormal clone. Abnormal clones were most common among patients who had refractory anemia with excess blasts (45%), refractory anemia with excess blasts in transition (60%), and chronic myelomonocytic leukemia (45%); they were least common among patients with refractory anemia (32%) and refractory anemia with ringed sideroblasts (21%). The two patients with refractory cytopenia had normal cytogenetic results. Each patient with the 5q - syndrome had a 5q-chromosome, as this is a prerequisite for the diagnosis. The two most common structural abnormalities were deletion of part of a chromosome 5 long arm (17 patients) and deletion of part of a chromosome 20 long arm (8 patients). Nonspecific structural abnormalities of chromosomes 1, 3, 6, and 17 were also common. The most common numeric abnormalities were monosomy 5 (7 patients), monosomy 7 (4 patients), loss of the Y chromosome (9 patients), and trisomy 8 (20 patients). No chromosome abnormalities were specifically associated with any PL/MDS classification.

Adult↗

Acute nonlymphocytic leukemia.

The discovery of cytosine arabinoside, and then the anthrocycline antibiotics, 6-thioguanine, vincristine, cyclophosphamide, and other drugs, has added to the armamentarium of known effective agents. The use of combination chemotherapy, the recognition of the need during induction for virtual marrow aplasia to obtain a remission, and recognition of the predilection of the disease for the central nervous system requiring prophylaxis constitute major advances. The impediment to long-term survival is the lack of effective maintenance therapy.

Acute Disease↗

Preleukemic syndromes and other syndromes predisposing to leukemia.

The myelodysplastic and myeloproliferative syndromes are syndromes in childhood that may precede leukemia. Clinical and biologic features are reviewed in this article. Although rare, they offer an unique opportunity to observe the evolution of leukemia and give clues that are helping us to understand the leukemogenic process.

Child↗

Use of bone-marrow culture in prediction of acute leukaemic transformation in preleukaemia.

Bone-marrow granulocyte-macrophage progenitor cell proliferation and regulatory factor (colony-stimulating activity; CSA) production were assessed at presentation and, if possible, subsequently in twenty-one patients with dysmyelopoiesis and less than 5% bone-marrow blasts. Seven patients underwent acute leukaemic transformation 1-35 months after the first marrow culture. Assay of bone-marrow endogenous CSA proved the most useful prognostic test. The rate of transformation in the seven patients with raised CSA at presentation was significantly greater (five transformed and one died at or before 4 months) than that in the fourteen patients with normal, low, or undetectable CSA (two transformed at 27 and 35 months). In one of the latter an increase in bone-marrow CSA occurred 6 weeks before transformation (serial marrow samples were not available in the other case). No other marrow culture feature measured, including the presence or absence of granulocyte-macrophage colony-forming cells and total clone numbers (colonies and smaller clusters) was as useful.

Adult↗

Acute myelogenous leukaemia with c-myc amplification and double minute chromosomes.

Cytogenetic analysis of bone-marrow cells from a woman with preleukaemia showed numerous mitoses with trisomy 4 and double minute chromosomes. These abnormalities were later seen in blood cells during subsequent acute myeloid leukaemia (AML). Complete remission was achieved with three courses of doxorubicin, cytosine arabinoside, and prednisone. A further clonal abnormality, trisomy 6, was seen in leukaemic cells after the first relapse. Analyses of total DNA from the peripheral-blood cells during relapse showed that the c-myc oncogene was amplified about 30-fold in the leukaemic cells. The N-myc, c-mos, and c-myb oncogenes showed only single-copy signals. On average about two copies of c-myc resided on each dmin chromosome. The finding of amplification of a cellular oncogene (c-myc) in fresh AML cells containing double minute chromosomes suggests that clonal evolution of some leukaemia cell populations may involve selection for increased dosage of oncogenes.

Chromosome Aberrations↗

Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy.

391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year follow-up the general risk of solid tumours was not increased.

Adult↗

Pancytopenia presenting with monosomy 7 which disappeared after immunosuppressive therapy.

Monosomy 7 syndrome in infant is considered as pre-leukemic condition of poor prognosis. However, it seems controversial recently, because some cases of monosomy 7 syndrome showed spontaneous remission. We report 2-year-old girl with severe pancytopenia, who presented with monosomy 7. Morphologically, there was little dysplasia in the trilineage hematopoiesis. Monosomy 7 clone of CD34 positive cells, bone marrow mononuclear cells (BMMNC), and peripheral nuclear cells was 4.0, 40, and 3.8%, respectively. Immunosuppressive therapy was effective along with the disappearance of monosomy 7 clone. WT1 mRNA expression was not increased in monosomy 7 clone. Pathogenesis of monosomy 7 and its relation to aplastic anemia is discussed.

Anemia, Aplastic↗

Development of minimally differentiated acute myeloblastic leukemia with novel isochromosome 18p and antecedent aplastic anemia.

We describe a case of acute myeloblastic leukemia with a novel isochromosome 18, i(18)(p10), preceded by aplastic anemia for six months. The patient is a cotton grower chronically exposed to pesticides. The significance of this chromosomal abnormality is unknown. The possible relationship to the preceding history of aplastic anemia and occupational pesticide exposure is speculated on. The possible mechanism of the association of acute leukemia and aplastic anemia is discussed.

Agricultural Workers' Diseases↗

Trisomy 6 as a primary karyotypic aberration in hematologic disorders.

We identified seven patients with hematologic disorders and trisomy 6 as the sole karyotypic aberration in bone marrow aspirates or unstimulated peripheral blood. Five patients were male and two were female; all were adults with ages ranging from 22 to 74 years. Three of the seven patients presented with manifestations of peripheral cytopenia. Their bone marrows were hypocellular with slight or no dysplastic changes and without an increase in blasts. One of these patients subsequently developed acute myeloid leukemia (AML-M1). The four remaining patients were initially diagnosed with AML--three consistent with French-American-British classification of M1 and M4 in the fourth patient. These results suggest that trisomy 6 is a nonrandom primary numerical anomaly of myeloid disorders. The association of cytopenia and hypoplastic bone marrow with trisomy 6 may constitute a new, distinctive variant among myelodysplastic syndromes.

Adult↗