Clinical implications of monosomy 7 in acute nonlymphocytic leukemia

A group of 18 patients with acute nonlymphocytic leukemia and the chromosomal aberration monosomy 7 in their bone marrow cells was compared to a group of control patients with the same disease but normal bone marrow chromosomes. The monosomy 7 group of patients had a higher incidence of fever and infections, and a higher white blood cell and granulocyte count compared to the control group at the time of diagnosis. The clinical difference between the groups continued over the first month of hospitalization. Complete remission was obtained in 12% of the monosomy 7 group and in 59% of the control group. Survival was clearly longer in the control group of patients. Monosomy 7 of the bone marrow in acute nonlymphocytic leukemia is therefore to be considered a bad prognostic sign.     

Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome

Clinical, cytomorphologic, and cytogenetic investigations were carried out in a series of 76 secondary MDS and ANLL. Chromosome abnormalities were more frequent in patients with a history of multiple myeloma or macroglobulinemia (92%) and myeloproliferative disorders (82%) than in patients with previous breast cancer (40%). The secondary hematologic malignancies were mostly a trilineage bone marrow disorder. The most commonly found cytogenetic anomaly was monosomy 7, followed by total or partial loss of chromosome 5. In addition six other chromosomes, i.e., chromosome 3, 8, 9, 12, 17, and 21 seemed to be consistently involved in the pathogenetic mechanisms of secondary leukemia and MDS.     

Chronic myeloid leukemia and interferon-alpha: a study of complete cytogenetic responders.

Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-alpha alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-alpha treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.     

Leukaemic Intermediate Lymphocytic Lymphomas: Analysis of Twelve Cases Diagnosed by Morphology

Twelve cases of leukaemic intermediate diffuse lymphocytic lymphoma (ILL), diagnosed by morphology, were analysed. The morphology of the ILL cells was so typical that it allowed ready distinction from chronic lymphocytic leukaemia (CLL) and other related B cell disorders. All cases were of B derivation, had strong µ and x or λ immunoglobulin (Ig) staining, were CD5 and FMC7 positive and CD 10 negative. Cytogenetic abnormalities were found in 8 patients all having t(11;14)(q13;q32). DNA analysis revealed a relatively high incidence of hypoploidy. At diagnosis all the patients (9 males, 5 females; median age 68) had a low degree of absolute lymphocytosis but the disease was advanced and mostly widespread. The course of the disease appears to be aggressive and incurable with conventional combination chemotherapy.     

Simultaneous occurrence of 5q− and 21q− in refractory anemia with thrombocytosis

A 40-yr-old female with refractory anemia and thrombocytosis was shown to possess 5q? and 21q? chromosomal anomalies in the hematopoietic cells. The former anomaly was demonstrated to be a del(5)(q14q32) and the latter to be due to a t(11;21)(q25;q21). A similar translocation was shown to exist in the cells of another patient with essential thrombocytosis. Thus, we tentatively identify the 21q? as being due to a t(11;21).     

A randomized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia

Summary To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108g glycoprotein (group I) or 216g glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (> 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p=0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.