Dr. Francesco Albano is Assistant Professor at the Institute of Hematology – Faculty of Medicine and Surgery, University of Bari - Italy He received his training in Medicine and Surgery at the University of Bari, where he graduated with honours in 1996. As a postgraduated student in hematology he worked in the field of molecular cytogenetic of acute and chronic leukemia. In 2002 he postgraduated in Hematology at the University of Bari. In 2006 he earned his PhD in clinical immunology from the University of Bari. Dr. Albano is involved in postgraduate teaching at the school of hematology at the university of Bari; moreover he is teacher of hematology at the Faculty of Biotechnology at the University of Bari. He is the first or contributing author in about 40 peer-reviewed papers concerning hematological disorders. He has focused his research efforts on molecular cytogenetics of myeloproliferative syndromes and acute leukemia.
Abstract: Follicular lymphoma is the second most frequent type of non-Hodgkin's lymphoma in adults. The basic molecular defect consists of the t(14;18)(q32;q21) translocation, juxtaposing the B-cell lymphoma protein 2 gene BCL2 to the immunoglobulin heavy chain locus IGH@, and leading to the antiapoptotic BCL2 protein overproduction. Variations in the t(14;18) are rare and can be classified into two categories: (i) simple variants, involving chromosomes 18 and 2, or 22, in which the fusion partner of BCL2 is the light-chain IGK@ or IGL@; (ii) complex variant translocations occurring among chromosomes 14, 18 and other chromosomes. We report a follicular lymphoma case showing BCL2 overexpression, detected by immunohistochemistry and real-time quantitative PCR, consequently to the formation of a novel fusion gene between the 5' of the lymphoid nuclear transcriptional activator gene AFF3 at 2q11.2, and the 3' of BCL2. This case shows evidence, for the first time, of BCL2 overexpression consequently to the fusion of BCL2 to a non-IG partner locus.Oncogene advance online publication, 14 July 2008; doi:10.1038/onc.2008.214.
Abstract: Two cases of therapy-related acute myeloid leukemia showed complex karyotypes, including a small ring and a larger D-chromosome. Multicolor fluorescence in situ hybridization and bacterial artificial chromosome and fosmid clones showed that both ring chromosomes were composed entirely of material excised from chromosome 12. The deleted segment of 12 was found fused to the short arm of a D-group chromosome. We hypothesized that similar mechanisms were involved in both rearrangements. A fusion at the short arms of chromosome 12 and a D-group chromosome was accompanied by excision and ligation of the chromosome 12 pericentromeric region to form a small ring chromosome.
Abstract: This study aimed to identify which graft product subset of CD34+ cells might be the most predictive of early hematopoietic recovery following allogeneic peripheral SCT (allo-PBSCT). The relationship between the number of 'mature' subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD133-) and 'immature' subsets of CD34+ cells (CD34+/CD33-, CD34+/CD38-, CD34+/DR- and CD34+/CD133+) and early neutrophil and platelet engraftment were studied in a homogeneous series (for disease, pre transplant chemotherapy, conditioning regimen and GVHD prophylaxis) of 30 AML patients after allo-PBSCT from HLA-identical siblings. In our experience, the total CD34+/CD133+ cell number was inversely correlated with the days required for the recovery of 0.5 x 10(9)/l neutrophils (r=or-0.82, P=0.02) and platelets of 20 x 10(9)/l (r=or-0.60, P=0.06); this correlation was better than the total CD34+ cell dose and neutrophil (r=or-0.70, P=0.04) and platelet engraftment (r=or-0.56, P=0.07). We suggest that a high number of CD34+/CD133+ PBSC may be associated with faster neutrophil and platelet recovery; these findings may help to predict the repopulating capacity of PBSC in patients after allo-PBSCT, especially when a relatively low number of CD34+ cells is infused.
Abstract: We report a case of chronic eosinophilic leukemia (CEL), demonstrating for the first time: (i) the association of CEL with the 5'KIAA1509/3'PDGFRB fusion gene as a consequence of a t(5;14)(q33;q32); (ii) the molecular detection of this rearrangement in an extramedullary site; (iii) the cloning and sequencing of the KIAA1509 and PDGFRB genomic breakpoints. The 5'KIAA1509/3'PDGFRB fusion gene is predicted to encode a protein of 2059 amino acids. The genomic breakpoints were localized inside KIAA1509 intron 11 and PDGFRB intron 10. Sequence analysis in correspondence with these breakpoints revealed the presence of repetitive DNA, such Alu elements, which could promote chromosomal rearrangements.
Abstract: Pseudocentric fission is a rare event consisting of the splitting of one functional centromere into two new products, of which only one can give rise to a functionally competent kinetochore. We report here a pseudocentric fission event within the D5Z2 alphoid subset disrupting the centromeric region of chromosome 5 in a case of chronic myeloid leukemia (CML) after treatment with imatinib and interferon. The breakage generated unequal partitioning of alpha-satellite sequences between the two fission products. One product was inserted within the long arm of chromosome 12 at band 14.3, becoming the only functional centromere of chromosome der(5). The other fission product was rearranged to form a sandwich-like dicentric--but functionally monocentric--chromosome der(6), made up of material from chromosomes 5, 12, and 6. The intercentric distance on der(6) was shown to be largely >20 Mb. To our knowledge, this is the first pseudocentric fission event described in CML. Moreover, our results confirm the susceptibility to breakage of the centromeric region of chromosome 5.
Abstract: We carried out fluorescence in situ hybridization (FISH) studies on 18 Ph+ chronic myeloid leukemia (CML) cases with chromosome 22 genomic deletions with the Vysis BCR-ABL dual-color/dual-fusion probe (BCR-ABL DC/DF) to compare the hybridization patterns obtained with this approach to those obtained with the "home brew" BAC/PAC system. Our results are the following: chromosome 22 microdeletions less than 400 kilobases (Kb) were not detected by the BCR DC/DF probe; FISH analysis with the BCR DC/DF probe in cases bearing chromosome 22 microdeletions ranging from 400 to 700 Kb produced a faint signal on the der(9); and the BCR-ABL DC/DF FISH pattern was comparable to the one obtained by the home brew probe in the presence of a 900-Kb chromosome 22 microdeletion. Our home-brew FISH system represents an accurate method for revealing a subset of CML patients with der(9) microdeletions.
Abstract: The t(9;22)(q34;q11), generating the Philadelphia chromosome, is found in more than 90% of patients with chronic myelocytic leukemia (CML). Deletions adjacent to the translocation breakpoint on the derivative chromosome 9 have been described by several groups. These studies revealed two primary points: (1) genomic microdeletions were concomitant with the t(9;22) rearrangement; and (2) the location of the deleted sequence was centromeric to ABL and telomeric to BCR genes. We report on a detailed molecular cytogenetic characterization of chromosomal rearrangements in two CML patients bearing a complex variant t(9;22) and insertions of chromosome 22 sequences in 9q34. Our study shows that the location of the deleted sequences was downstream of the ABL gene and that genomic microdeletions were concomitant with the ins(9;22)(q34;q11q11) rearrangement.
Abstract: BACKGROUND AND OBJECTIVES: Acute promyelocytic leukemia (APL) is characterized by leukemic cells blocked at the promyelocytic stage of granulocytic differentiation. To date, it is still not clear whether CD34 expression identifies a subset of APL patients with peculiar characteristics. We, therefore, conducted a detailed analysis of CD34 expression at diagnosis in 136 adults with de novo APL. DESIGN AND METHODS: We investigated 136 newly diagnosed APL patients from four Italian Institutions. All 136 cases were tested for CD34 and CD2 expression: 124 (91%) cases were classified as hypergranular (M3) and 12 (9%) as the hyporgranular M3 variant (M3v). The parameters considered were white blood cell (WBC) and platelet counts, hemoglobin levels, percentage of peripheral blood leukemic promyelocytes (PBLP), CD15, CD56 and HLA-DR expression, and the PML/RARalpha isoform, to assess their relationship with CD34 and CD2 expression. RESULTS: CD34 expression was associated with the M3v subtype and higher proportion of HLA-DR+ and CD2+ cases. Moreover, compared with CD34- APL patients, CD34+ APL patients had a significantly higher percentage of PBLP at presentation, were more frequently female and had a higher proportion of bcr3 expression. Among the 136 APL cases, 24 (17.6%) and 80 (58.8%) were identified as CD34+CD2+ and CD34-CD2-, respectively. The two groups showed statistically significant differences in terms of M3vfrequency, WBC and platelet counts, percentage of PBLP, and bcr3 expression. Moreover, the CD34+CD2+ group showed a higher proportion of CD34+ and bcr3 isoforms compared to the M3v cases. There were no differences between the two groups in terms of complete remission, overall survival and disease-free survival. INTERPRETATION AND CONCLUSIONS: Our findings suggest that immunophenotypic analysis can distinguish a subset of APL patients with different biological characteristics.
Notes: 1592-8721 (Electronic) xD;Comparative Study xD;Journal Article
Abstract: Six patients with de novo acute myeloid leukemia (AML) and a t(2;3)(p15-21;q26-27) were identified among approximately 1000 cases enrolled in the GIMEMA trial. The t(2;3) was the sole anomaly in three patients, whereas in three cases monosomy 7, trisomy 15 and 22, and trisomy 14 represented additional aberrations. No cryptic chromosome deletions at 5q, 7q, 12p, and 20q were observed. One patient carried a FLT3 D835 mutation; FLT3 internal tandem duplication (ITD) was not detected in three patients tested. Characterization of the translocation breakpoints using a 3q26 BAC contig specific for the PRDM3 locus showed that the breakpoints were located 5' to EVIl as follows: within myelodysplatic syndrome (MDS) intron 1 (# 3), between MDS1 exons 2 and 3 in three patients (# 1, 2, 4) with a 170bp cryptic deletion distal to the breakpoint in one (# 2), and in a more centromeric position spanning from intron 2 to the 5' region of EVI1 (# 6, 5). A set of 2p16-21 BAC probes showed that the breakpoints on chromosome 2p were located within BCL11A in two separate regions (# 1, 4 and # 2-5), within the thyroid adenoma-associated (THADA) gene (# 6) or distal to the ZFP36L2 locus (# 3). Regulatory elements were present in proximity of these breakpoints. RACE PCR studies revealed a chimeric transcript in 1/6 patient analyzed, but no fusion protein. Quantitative PCR showed a 21-58-fold over-expression of the EVIl gene in all cases analyzed. The patients showed dysplasia of at least two myeloid cell lineages in all cases; they had a low-to-normal platelet count and displayed an immature CD34+ CD117+ immunophenotype. Despite intensive chemotherapy and a median age of 43 years (range 36-59), only two patients attained a short-lived response; one patient is alive with active disease at 12 months, five died at 4-14 months. We arrived at the following conclusions: (a) the t(2;3) is a recurrent translocation having an approximate 0.5% incidence in adult AML; (b) breakpoints involve the 5' region of EVIl at 3q26, and the BCL11A, the THADA gene or other regions at 2p16.1-21; (c) cryptic deletions distal to the 3q26 breakpoint may occur in some cases; (d) the juxtaposition of the 5' region of EVIl with regulatory elements normally located on chromosome 2 brings about EVI1 overexpression; (e) clinical outcome in these cases is severe.
Abstract: In the present paper, we report a molecular cytogenetic study of 1q abnormalities associated with t(8;14)(q24;q32) in an adult common B acute lymphoblastic leukemia case with FAB-L2 morphology. The use of appropriate molecular cytogenetic probes allowed us to detect 13 different subclones showing heterogeneous chromosome 1 abnormalities. A complex pattern of rearrangements consisting of translocations, duplications, and inversions was observed. Breakage-fusion-bridge cycle and jumping translocation are hypothesized to have been involved in generating the large number of aberrations we detected.
Abstract: The t(8;21)(q22;q22) rearrangement is observed in about 15% of acute myelocitic leukemia (AML) cases, while variant t(8;21) translocations are detected in 6-10% of AML patients positive for the 5'RUNX1/3'CBFA2T1 fusion gene. We report a detailed molecular cytogenetic analysis of a four-way variant t(8;11;16;21)(q22;q14;q12;q22) performed by fluorescence in situ hybridization with specific BAC and PAC clones. The study demonstrated the loss of several megabases belonging to chromosomes 11 and 16 whereas no deletion was detected on der(21). These findings suggest that a precise breakpoint characterization could identify submicroscopic genomic deletions whose meaning remains to be defined.
Abstract: In the present paper we report pericentric chromosome 8 inversions in two (2.4%) of 82 acute myeloid leukemia (AML) cases characterized by the 5'RUNX1/3'CBFA2T1 fusion gene. Molecular cytogenetic characterization was achieved using appropriate bacterial artificial chromosome (BAC) and P1 artificial chromosome (PAC) probes in fluorescence in situ hybridization (FISH) experiments. In these two cases the fusion gene was detected on the der(8) short arm, resulting from a pericentric chromosome 8 inversion followed by a t(8;21) rearrangement. These results suggest that heterogeneous mechanisms can lead to the generation of the 5'RUNX1/3'CBFA2T1chimeric gene.
Abstract: Translocation t(8;21)(q22;q22) is a common karyotypic abnormality detected in about 15% of acute myeloid leukemia (AML) cases. The rearrangement results in fusion of the RUNX1 (also known as AML1) and CBFA2T1 (also known as ETO) genes, generating a 5'RUNX1/3'CBFA2T1 transcriptionally active fusion gene on derivative chromosome 8, but some cases with ins(21;8) and ins(8;21) have been observed. However, a detailed breakpoint characterization of the insertion events has never been reported. In the present article, we describe six insertion events among 82 (7.3%) AML cases characterized by the RUNX1/CBFA2T1 fusion. Using FISH experiments with appropriate bacterial artificial chromosome (BAC) and P1 artificial chromosome (PAC) probes, we were able to perform a detailed molecular cytogenetic characterization of one case with ins(8;21) and five with ins(21;8). Our analysis revealed that insertions generating the 5'RUNX1/3'CBFA2T1 gene showed variable breakpoints; the size of the inserted elements ranged from 2.4 to 44 Mb.
Abstract: The t(9;22)(q34;q11) is evident in more than 90% of patients with chronic myelocytic leukemia (CML) and gives rise to the Philadelphia chromosome (Ph). Approximately 5%-10% of CML patients show variant translocations involving other chromosomes in addition to chromosomes 9 and 22. In some variant translocations, additional material is transferred on der(22), resulting in a masked Ph chromosome. In this paper, we report two apparently Ph-negative (Ph-) CML cases showing a t(7;9;22)(q22;q34;q11) and a t(8;9;22)(q12;q34;q11), respectively. A detailed molecular cytogenetic characterization was performed by fluorescence in situ hybridization (FISH), which disclosed the presence of the 5'BCR/3'ABL fusion gene on the der(7) and der(8) chromosomes, respectively. Derivative (22) appeared as a masked Ph chromosome in both cases. FISH analysis with appropriate BAC/PAC clones allowed us to precisely characterize the complex chromosomal rearrangements that were not detected by conventional cytogenetic analysis.
Abstract: Genomic deletions on the derivative chromosomes bearing the reciprocal fusion gene have recently been reported in chronic myelocytic leukemia (CML). We here describe a CML case with a variant rearrangement t(9;22;11)(q34;q11;q13) showing the loss of chromosome 11 sequences in addition to der(9) deletions. Known tumor suppressor genes involved in apoptosis and in the control of cell proliferation were found to be mapped to the lost sequences. Our findings indicate that genomic deletions may occur also on the third derivative chromosome in variant t(9;22).
Abstract: It has recently been postulated that the absence of a single tumor suppressor gene (TSG) allele can provide a selective advantage for an emerging tumor cell. We have characterized the precise extension of the deletion on der(9) in 20 chronic myeloid leukemia (CML) cases using FISH analysis with an appropriate set of BAC/PAC probes to attempt a better definition of TSGs encompassed by these genomic deletions. Chromosome 9 deletions on the der(9) were detected in 15 (75%) cases; the TSG PTGES gene was lost in 11 (73%) cases. Chromosome 22 deletions on der(9) were found in 18 (90%) of the analysed cases; two TSGs were found located inside the deleted sequences of chromosome 22: SMARCB1 and GSTT1. These TSGs were found deleted in 16 (89%) cases bearing deletions of chromosome 22. Fourteen (70%) patients were treated with IFN-alpha therapy: 12 did not obtain complete haematologic remission (CHR) and 2 were not evaluable for response. Therefore, the patients did not respond to the IFN-alpha treatment started Glivec obtaining CHR and major cytogenetic response (MCR). The observation that deletions on der(9) are associated with the loss of TSGs suggests their possible involvement in the CML outcome, mediated by a haplo-insufficiency mechanism.
Abstract: The EVI1 proto-oncogene encodes a nuclear zinc finger protein that acts as a transcription repressor factor. In myeloid leukemia it is often activated by chromosomal rearrangements involving band 3q26, where the gene has been mapped. Here we report two leukemia cases [a chronic myeloid leukemia blast crisis (CML-BC) and an acute myeloid leukemia (AML) M4] showing a t(3;7)(q26;q21) translocation in a balanced and unbalanced form, respectively. Fluorescent in situ hybridization (FISH) analysis revealed that both patients showed a breakpoint on chromosome 3 inside the clone RP11-33A1 containing the EVI1 oncogene and, on chromosome 7, inside the clone RP11-322M5, partially containing the CDK6 oncogene which is a D cyclin-dependent kinase gene, observed to be overexpressed and disrupted in many hematological malignancies. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed overexpression of EVI1 in both cases, but excluded the presence of any CDK6/ EVI1 fusion transcript. CDK6 expression was also detected. Together, these data indicate that EVI1 activation is likely due not to the generation of a novel fusion gene with CDK6 but to a position effect dysregulating its transcriptional pattern.
Abstract: Several studies in childhood acute lymphoblastic leukemia (ALL) have documented that molecular detection of minimal residual disease (MRD) based on screening for T-cell receptor and immunoglobulin gene rearrangements can identify patients at a high risk of relapse. In our experience, evaluation of MRD in adult ALL can help to identify high risk patients.
Abstract: The characteristics of the very rare non-treatment-related chronic myeloid leukemia (nTr-CML) cases have never before been analyzed. The literature up to December 2002 was screened using the Medline database to identify cases of Tr-CML and nTr-CML. We considered five cases with nTr-CML identified among 270 newly diagnosed CML at our Department. Our report thus considers nine cases with nTr-CML compared to 77 affected by Tr-CML as a secondary neoplasm. The median age at the appearance of the first tumor was higher in nTr-CML patients compared to that of the Tr-CML group (P<0.0001). The median age at CML diagnosis was significantly higher in the nTr-CML than in the Tr-CML group (P<0.0001). The proportion of hematological malignancies as first tumor type was not different in the two groups (44% in nTr-CML versus 56% in Tr-CML). Our study underlines that nTr-CML as a second malignancy is a rare entity associated with elderly age.
Abstract: The t(9;22)(q34;q11), generating the Philadelphia chromosome (Ph), is found in more than 90% of patients with chronic myeloid leukemia (CML) and in 15-30% of adults with acute lymphoblastic leukemia (ALL). Different groups have recently described the presence of large genomic deletions adjacent to the translocation breakpoint on the derivative chromosome 9 in 9-16% of CML patients. In the present paper, we report a FISH study of 45 Ph+ adult ALL patients with the aim of investigating the presence of deletions on derivative chromosome 9. In four (9%) of 45 cases, all showing an M-bcr, we detected deletions on der(9). The frequency of deletions we observed is similar to that reported in CML patients. The association of an M-bcr breakpoint and deletions appears significant (P=0.03). Some authors have suggested a very low incidence of der(9) deletions in ALL. This discrepancy can be explained by taking into account the low percentage of M-bcr ALL patients in the latter study (18%) compared to the present one (44%).
Abstract: The Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML) and is observed in more than 90% of CML cases. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22). Deletions adjacent to the translocation junction on the derivative chromosome 9 were recently described by different groups. The deletions may identify a subgroup with a worse prognosis. The presence of similar deletions on the third derivative other than the 9 and 22 chromosomes in CML with variant translocation has never been investigated. We studied three cases of CML variants showing relatively large deletions on the third chromosome involved in the translocation. Known tumor-suppressor genes (TSGs) or genes involved in signal transduction and in the modulation of cell proliferation were found to be located inside these deleted regions. As an alternative to Knudson's two-hit model, the "haplo-insufficiency" hypothesis suggests that the deletion of a single allele of a TSG can play an important role in tumor progression. Our findings suggest that great attention should be paid to the molecular cytogenetic characterization of variant t(9;22) CML patients to unveil fully the biological heterogeneity of CML.
Abstract: We report a fluorescent in situ hybridization (FISH) study on 34 patients with acute promyelocytic leukemia. The study was designed to detect microdeletions in the derivative chromosome 17 which is the result of a reciprocal translocation t(15;17). No deletion was found.
Abstract: Deletions adjacent to the 9/22 translocation breakpoint on the derivative chromosome 9 have recently been described in a substantial number of chronic myeloid leukemia (CML) cases, but their extension has not been characterized in detail. Using FISH with an appropriate set of BAC/PAC probes, we have characterized the deletion in 10 CML cases, identified by screening 71 patients at diagnosis. Five patients showed a complex chromosome rearrangement and 3 of them were deleted. The size of the deletion was variable, ranging from few hundreds kb to 8 Mb. A minimally deleted region on both chromosomes 9 and 22 was identified and was found to contain the ASS gene on chromosome 9 and IGLL1 on chromosome 22.
Abstract: Chronic lymphocytic leukemia (CLL) associated with myeloid antigens on the surface of B neoplastic cells is a recently identified immunologic variant confined to patients with CD5 negative B-CLL. We describe the case of a 61-year-old female diagnosed with CD5(-), CD13(+) B-CLL with a tetrasomy 3q revealed by fluorescence in situ hybridization analysis, in addition to trisomy 18. To our knowledge, this is the first reported case of B-CLL with this kind of cytogenetic abnormality.
Abstract: We describe a novel chromosomal aberration acquired in blast crisis (BC) in a patient affected by Philadelphia-positive chronic myeloid leukemia (CML). Conventional cytogenetic studies at onset showed a classic t(9;22)(q34;q11.2) in all bone marrow cells, confirmed by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction (b3a2) analysis. In BC, the malignant clone developed a new additional cytogenetic abnormality consisting of a deletion of chromosome 21. To our knowledge, this is the first case of del(21) reported in literature associated with BC CML. The use of an appropriate set of BAC/PAC clones restricted the breakpoint to an interval of approximately 100 kb. Sequence analysis did not reveal any known gene in this interval. Oncosuppressor genes distal to the breakpoint could be hypothesized to be involved in the progression of disease toward BC. Identification of new chromosome abnormalities in CML may allow further understanding of specific molecular events leading to disease evolution.
Abstract: We report a case of positive Philadelphia chromosome adult acute lymphoblastic leukaemia with a novel unbalanced translocation t(17;19), leading to trisomy of 17q21-qter. The patient did not obtain complete haematological response and died a few months after diagnosis. The significance of the 17q21-qter trisomy, resulting from this novel translocation, and its possible role in the progression of the leukaemia is discussed.
Abstract: PURPOSE: Recent reports of extramedullary disease (EMD) at recurrence in acute promyelocytic leukemia (APL) have raised increasing concern about a possible role of retinoic acid (RA) therapy. PATIENTS AND METHODS: We analyzed the risk of developing EMD localization at relapse in APL patients enrolled onto two consecutive studies of the Gruppo Italiano Malattie Ematologiche dell'Adulto. The studies investigated chemotherapy alone (LAP0389) versus RA plus chemotherapy (AIDA). RESULTS: When all relapse types were taken into account, 94 (51%) of 184 patients and 131 (18%) of 740 patients who attained hematologic remission underwent relapse in the LAP0389 and AIDA studies, respectively (P < .0001). EMD localization was documented in five (5%) of 94 and 16 (12%) of 131 patients (P = .08). Hematologic and/or molecular relapse was diagnosed concomitantly in all but two patients with EMD in the AIDA study. For patients in the LAP0389 and AIDA series, the probability of EMD localization of any type at relapse was 3% and 4.5%, respectively (P = .79), while the probability of CNS involvement was 0.6% and 2% (P = .28). No significant differences were found with regard to mean WBC count and promyelocytic leukemia/retinoic acid receptor-alpha junction type in comparisons of patients with EMD and hematologic relapse. CONCLUSION: APL patients receiving all-trans retinoic acid in addition to chemotherapy have no increased risk of developing EMD at relapse as compared with those treated with chemotherapy alone.
Abstract: Retinal abnormalities (RA) are very frequently observed in adult patients with acute myeloid leukemia (AML), but the clinical significance of these findings has not been fully investigated. We examined the fundus oculi in a cohort of 122 adult patients with AML at presentation and analyzed some clinical and biological features to assess whether there was any association with RA. For this purpose, we subdivided the patients into two groups according to the presence or absence of RA (groups 1 and 2, respectively). We considered current laboratory parameters such as white blood cell (WBC) count, hemoglobin (Hb), platelets and serum lactate dehydrogenase (LDH). Moreover, we subdivided the patients into two groups according to age <60 (group A) or > or =60 years (group B) to evaluate a possible association between RA and response to treatment and/or overall survival (OS). In our series, a higher median age and a lower Hb value were associated with group 1 (p = 0.001 and p = 0.04, respectively); the median LDH value was 812 U/l (range 224-5,551) and 607 (range 181-5,244) for groups 1 and 2, respectively (p = 0.02). There was no association between RA and karyotypic alterations. In terms of outcome, in group A (<60 years), 80% patients who achieved complete remission (CR) were in group 2 vs. 13% nonresponders (NR) (p < 0.0001). Median OS of group 2 patients was 49.7 months compared with 7.2 months for those in group 1 (p = 0.002). In group B, 58% patients who achieved CR were in group 1 vs. 15% NR (p < 0.006). Median OS of patients in group 2 was 14.6 months compared with 2.9 months in group 1 (p = 0.02). Our data show that RA are significantly associated with some biological features and with shorter OS in AML patients and this parameter seems to be an effective clinical sign of poor prognosis in terms of CR.
Abstract: BACKGROUND AND OBJECTIVES: In adult acute myeloid leukemia (AML), a variety of clinical and biological parameters have been examined for their potential value in predicting treatment response. Early response to induction therapy could be an important prognostic factor in this disease. DESIGN AND METHODS: We studied the relationship between reduced blasts in bone marrow aspirate on the 14th day (BMA14th) of induction chemotherapy and treatment outcome in 198 adult AML patients of whom 124 were < 60 years old (group A) and 74 > or = 60 years old (group B). Receiver operating characteristic curve analysis was used to assess the prognostic performance of BMA14th. Using the percentages of blasts of < or = 22% and < or = 15% as criteria for predicting treatment outcome gave the highest accuracy in terms of sensitivity and specificity in groups A and B, respectively. RESULTS: In group A, of 97 patients with a BMA14th < or = 22%, 77 (79%) achieved complete remission (CR), whereas of 27 patients with a BMA14th > 22%, 22 (81%) were non-responders (NR) (p < 0.0001). The test sensitivity and specificity were 93.9% and 71.4%, respectively. In group B, of 27 patients with a BMA14th < or = 15%, 18 (67%) achieved CR, whereas of 47 patients with a BMA14th >15%, 38 (81%) were NR (p = 0.0001). The test sensitivity and specificity were 66.7% and 80.9%, respectively. INTERPRETATION AND CONCLUSIONS: Our data suggest that BMA14th may be a predictive test for CR, helping to identify NR patients early in their disease. Further studies are needed to establish the practical implications of the results of our study.
