Induction and prevention of micronuclei and chromosomal aberrations in cultured human lymphocytes exposed to the light of halogen tungsten lamps.

Previous studies have shown that the light emitted by halogen tungsten lamps contains UV radiation in the UV-A, UV-B and UV-C regions, induces mutations and irreparable DNA damage in bacteria, enhances the frequency of micronuclei in cultured human lymphocytes and is potently carcinogenic to the skin of hairless mice. The present study showed that the light emitted by an uncovered, traditional halogen lamp induces a significant, dose-related and time-related increase not only in micronuclei but also in chromosome-type aberrations, such as breaks, and even more in chromatid-type aberrations, such as isochromatid breaks, exchanges and isochromatid/chromatid interchanges, all including gaps or not, in cultured human lymphocytes. All these genotoxic effects were completely prevented by shielding the same lamp with a silica glass cover, blocking UV radiation. A new model of halogen lamp, having the quartz bulb treated in order to reduce the output of UV radiation, was considerably less genotoxic than the uncovered halogen lamp, yet induction of chromosomal alterations was observed at high illuminance levels.

A new chromosome translocation (3;21) in M2 acute lymphocytic leukemia.

High-resolution chromosome banding studies were carried out on leukemic cells from a young patient with acute nonlymphocytic leukemia (ANLL), M2 of the FAB classification. A new chromosomal abnormality involving a translocation between chromosomes 3 and 21 was observed, i.e., t(3;21)(p14;q22). A complete remission was never obtained in spite of aggressive chemotherapy and the patient died 8 months after diagnosis.

Bone marrow transplantation for chronic granulocytic leukemia.

Thirty patients with chronic granulocytic leukemia (CGL), were given cyclophosphamide 60 mg/kg on each of 2 consecutive days, followed by total body irradiation (TBI) 10 Gy and an HLA-identical bone marrow transplant (BMT). Eleven patients were in the accelerated phase of their disease (CGLacc) or in second/secondary chronic phase (CGL-2CP), with a median age of 33 years: four patients died of transplant related complications, and four of recurrent leukemia; three patients are alive and well 19, 31, 33 months from BMT. The actuarial 33-month survival is 27%. The actuarial relapse rate is 50%. Nineteen patients were in their first chronic phase (1CP), with a median age of 32 years: three died of graft versus host disease (GvHD), two of infection, and two of acute respiratory distress syndrome (ARDS); 12 are alive and well 6 to 29 months post-BMT. The actuarial 29-month survival is 63%. The actuarial survival of patients younger than 30 years is 63%, compared to 62% for patients older than 30 (P = 0.1). The survival of patients grafted within or after 24 months from the onset of CGL is respectively 87% and 45% (P = 0.04). None of the patients grafted in 1CP had a true hematologic-cytogenetic relapse. The Ph' chromosome was detected on one occasion in two patients 12, 13 months post-BMT: they both remain hematologically normal and Ph1-negative 3 to 6 months later, after discontinuation of cyclosporin A. This study confirms that survival exceeding 60% can be obtained in CGL in the first chronic phase, whereas less than 30% of patients will survive if grafted in accelerated, second/secondary chronic phase, mainly because of leukemic relapse. The duration of the disease seems to be relevant to the outcome of the transplant. The effect of post-transplant immunosuppression, in our case cyclosporin A, on the interaction between normal and Ph1-positive hemopoietic cells, may deserve further attention.

Cytogenetic abnormalities in patients with severe aplastic anemia.

BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.

Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia.

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.