Analysis of prognostic factors in patients with refractory anemia with excess of blasts (RAEB) reclassified according to WHO proposal.

The WHO classification subdivides the FAB RAEB category into RAEB-1 (bone marrow (BM) blasts <10%, peripheral blasts <5%) and RAEB-2 (bone marrow blasts >10% and peripheral blasts >5%). We reclassified according to WHO criteria 228 RAEB patients and analysed them in terms of haematological, karyotypic and prognostic features. We used the database of 680 MDS patients referred to our Institution from 1990 to 2000. Clinical features at presentation, such as sex, age, leukocyte count, polymorphonuclear cell count (PMN), platelet count, haemoglobin level, presence of one or more lineage dysplasia were tested in univariate and multivariate analysis in the two groups of RAEB-1 and RAEB-2 reclassified patients. In multivariate analysis we identified prognostic significant factors in the two patient groups, which consisted of age >70 years and platelet count <100 x 10(9)l(-1) for RAEB-1 category, while for RAEB-2 group parameters negatively influencing survival and risk of progression were haemoglobin <10g/dl, platelet count <100 x 10(9)l(-1), bone marrow blastosis >15% and complex karyotype. We also found differences in cytogenetic data (more balanced translocations and complex karyotypes in RAEB-2 group, p=0.02), and in survival (23.3 months in RAEB-1 vs. 16.1 months in RAEB-2 group, p=0.001). WHO classification provides valuable prognostic information for RAEB patient population, and can identify those subjects with more unfavourable prognosis who should be offered alternative therapeutic strategies.

Incidence and significance of cryptic chromosome aberrations detected by fluorescence in situ hybridization in acute myeloid leukemia with normal karyotype.

To better define the incidence and significance of cryptic chromosome lesions in acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies were performed in interphase cells and, when appropriate, in metaphase cells and in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and 27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were tested using probes detecting the following anomalies: -5, -7, +8, deletions of 5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype in more than 20 cells and tested negative for the common AML-associated fusion genes. No patient in group A was found to carry occult chromosome anomalies, whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33-60% interphase cells. Metaphase cells showed only one hybridization signal at 5q31 (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8 in interphase cells. The majority of blast cells (76-94%) carried the chromosome anomaly in all cases; erythroid involvement in a minority of cells was seen in three patients. In group B, the presence of occult chromosome anomalies was associated with exposure to myelotoxic agents in the workplace (5/8 cases vs 3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12, P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome deletions in the order of a few hundred kb magnitude may be found in a fraction of elderly AML or MDS-related AML and not in de novo adult AML with normal karyotype; (2) these chromosome lesions are usually represented by submicroscopic rearrangements; (3) they display a specific pattern of cell-lineage involvement arguing in favor of their role in the outgrowth of the leukemic blast cells; (4) they are associated with a history of exposure to myelotoxic agents in the workplace and, possibly, with resistance to induction treatment.

Acute myeloid leukemia and lung cancer occurring in a chronic lymphocytic leukemia patient treated with fludarabine and autologous peripheral blood stem-cell transplantation.

An increased incidence of different malignancies associated to chronic lymphocytic leukemia (CLL) has been reported. The association of CLL and acute leukemia is a rare event described in < 1% of CLL, the type of acute leukemia being either from the lymphoid or more often from the myeloid lineage. The coexistence of acute myeloid leukemia (AML) and CLL in the same patient has been occasionally reported. Most of these cases have been associated with the administration of chemotherapy or radiotherapy for CLL, suggesting that the former may be a secondary leukemia. On the other hand, CLL could precede, but could also be diagnosed at the same, or delayed time as AML, suggesting the presence of other leukemogenic factors. We describe the exceptional development of AML and lung cancer in a patient with previously diagnosed CLL in minimal residual disease status after fludarabine treatment followed by autologous peripheral blood stem-cell transplantation.