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Seval Türkmen,
Bernd Timmermann,
Gesine Bartels,
Daniela Gröger,
Claus Meyer,
Stefan Schwartz,
Claudia Haferlach, Harald Rieder,
Nicola Gökbuget,
Dieter Hoelzer,
Rolf Marschalek,
Thomas Burmeister
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ABSTRACT: While the MLL "recombinome" is relatively well characterized in B-cell precursor acute lymphoblastic leukemia (BCP ALL), available data for adult acute T-lymphoblastic leukemia (T-ALL) are scarce. We performed fluorescence in situ hybridization (FISH) for an MLL split signal on 223 adult T-ALL samples obtained within the framework of the German Multicenter ALL 07/2003 therapy trial. Three biphenotypic leukemias (T-ALL/AML) were also included in the analysis. Samples showing any alteration by FISH were further investigated to characterize the MLL aberration. In addition, they were investigated for common genetic lesions known in T-ALL. Twenty-two cases (9.5%) showed an abnormal MLL signal by FISH analysis. Most of these appeared to be deletions or gains but in five cases (2.1%) a chromosomal translocation involving the MLL gene was identified. The translocation partners and chromosomal breakpoints were molecularly characterized. Three T-ALLs had an MLL-AF6/t(6;11) and two biphenotypic leukemias had an MLL-ELL/t(11;19). The chromosomal breakpoints in two of the MLL-AF6-positive cases were located outside the classical MLL major breakpoint cluster known from BCP ALL. In conclusion, the spectrum of MLL translocation partners in adult T-ALL much more resembles that of AML than that of BCP ALL and thus the mechanisms by which MLL contributes to leukemogenesis in adult T-ALL appear to differ from those in BCP ALL. Proposals are made for the diagnostic assessment of MLL fusion genes in adult T-ALL. © 2012 Wiley Periodicals, Inc.
Genes Chromosomes and Cancer 08/2012; 51(12):1114-24. · 3.31 Impact Factor
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Nicola Gökbuget,
Michael Kneba,
Thorsten Raff,
Heiko Trautmann,
Claus-Rainer Bartram,
Renate Arnold,
Rainer Fietkau,
Mathias Freund,
Arnold Ganser,
Wolf-Dieter Ludwig,
Georg Maschmeyer, Harald Rieder,
Stefan Schwartz,
Hubert Serve,
Eckhard Thiel,
Monika Brüggemann,
Dieter Hoelzer
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ABSTRACT: Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized methods and terminology in patients with Philadelphia chromosome-negative ALL. The cytologic complete response (CR) rate was 89% after induction phases 1 and 2. At this time point the molecular CR rate was 70% in 580 patients with cytologic CR and evaluable MRD. Patients with molecular CR after consolidation had a significantly higher probability of continuous complete remission (CCR; 74% vs 35%; P < .0001) and of overall survival (80% vs 42%; P = .0001) compared with patients with molecular failure. Patients with molecular failure without stem cell transplantation (SCT) in first CR relapsed after a median time of 7.6 months; CCR and survival at 5 years only reached 12% and 33%, respectively. Quantitative MRD assessment identified patients with molecular failure as a new high-risk group. These patients display resistance to conventional drugs and are candidates for treatment with targeted, experimental drugs and allogeneic SCT. Molecular response was shown to be highly predictive for outcome and therefore constitutes a relevant study end point. The studies are registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.
Blood 03/2012; 120(9):1868-76. · 9.90 Impact Factor
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ABSTRACT: Burkitt lymphoma and a subset of diffuse large B-cell lymphomas are characterized by chromosomal alterations affecting the MYC oncogene on 8q24. In most cases MYC is found juxtaposed to the immunoglobulin heavy chain (IGH) gene locus. Translocations to the immunoglobulin kappa (IGK) gene locus on 2p11 are observed in around 5-10% of cases. Little data exist on the molecular mechanisms leading to this aberration. The chromosomal breakpoints on chromosome 8 have been found dispersed over a large area 3' of MYC. In order to obtain a better understanding of this chromosomal translocation we developed a long-distance inverse (LDI) PCR method for the identification of chromosomal translocations affecting the IGK locus. We investigated a number of cytogenetically mostly uncharacterized high-grade lymphoma samples and identified a MYC-IGK juxtaposition in seven patients and three t(2;8)-positive cell lines. The chromosomal breakpoints were molecularly characterized and analyzed. The linear distance of the breakpoints on chromosome 8 to MYC ranged from some 100 bp to more than 0.5 MB. The reciprocal translocated allele could be characterized in the majority of cases. This study represents the largest series of t(2;8)-positive cases analyzed so far. The LDI PCR method developed here should also be useful for the analysis of chromosomal translocations affecting the IGK locus in general.
Genes Chromosomes and Cancer 11/2011; 51(3):290-9. · 3.31 Impact Factor
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Rüdiger Hehlmann,
David Grimwade,
Bengt Simonsson,
Jane Apperley,
Michele Baccarani,
Tiziano Barbui,
Giovanni Barosi,
Renato Bassan,
Marie C Béné,
Ute Berger, [......],
Per Ljungman,
Ulrich Mansmann,
Dietger Niederwieser,
Gert Ossenkoppele,
José M Ribera, Harald Rieder,
Hubert Serve,
Petra Schrotz-King,
Miguel A Sanz,
Susanne Saussele
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ABSTRACT: The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.
Haematologica 11/2010; 96(1):156-62. · 6.42 Impact Factor
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ABSTRACT: In order to assess any correlation between MDR-1 expression and chromosomal aberrations, and to define their impact on clinical outcome in newly diagnosed AML pts, we investigated bone marrow and peripheral blood samples of 49 consecutive pts admitted to our hospital. Monosomy 7, trisomy 8 and 5q-were evaluated by means of interphase fluorescence in situ hybridization (FISH). Monosomy 7 was present in 6 pts, trisomy 8 in 5 pts, and 5q-in 6 pts. More than one aberration was seen in 7 pts. Chromosomal aberrations were mostly found in older pts (12/14 > 60 years; p=0.03) and in pts with CD34 positive leukemic blasts (13/14 coexpressed CD34; p=0.0004). In 25 pts also standard G-banding analysis was performed leading to concordant results regarding chromosomes 7, 8 and 5. Flow cytometry identified MDR-1 positivity (MDR+) in 16 pts. MDR-1 expression appeared to be a characteristic feature in CD34+ AML (12/16 were CD34+ and MDR+ pts; p=0.013). No correlation, however, was found between chromosomal aberrations and MDR-1 expression. Pts with aberrations of either chromosomes 7, 8 or 5 detected by FISH (FISH+) were predominantly resistant to induction therapy (6/8 pts, p=0.004). A lower rate of complete remission (CR) was also seen in pts with MDR-1 expression (p=0.006). MDR+/FISH+ pts (n=3) were all refractory to remission induction, while all MDR-/FISH-pts (n=19) achieved CR (p=0.0006). MDR-1+ as well as pts with aberrations of chromosomes 7, and 5(q) showed a significantly decreased probability of overall survival. In conclusion, MDR-1 expression as well as abnormalities of chromosomes 7, and 5(q) predict poor clinical outcome in AML. The identification of these prognostic factors provides useful information for risk adapted treatment strategies.
Leukemia and Lymphoma 06/2009; 40(5-6):613-623. · 2.58 Impact Factor
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ABSTRACT: Expression of CD56 has been associated with poor prognosis in acute myeloid leukemia and aggressive lymphoma.
We analyzed the impact of CD56 expression in a cohort of 452 newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients; clinical data were available for 306 patients. Treatment was according to the GMALL study protocols 06/99 and 07/03 stipulating stratification into standard (thymic T-ALL) and high risk (pre- and mature T-ALL) groups.
CD56 expression was detected in 63/452 (13.9%) patients. CD56(+) T-ALL were predominantly of non-thymic (pre-T 35%, mature 41%) immunophenotypic subtypes, whereas 53% of the CD56(-) cases were thymic T-ALL (p=0.00002). CD13, CD33, CD34 and HLA-DR were significantly more frequently expressed. A clonal T-cell receptor rearrangement was detected in 22/23 CD56(+) ALL. No major clinical differences were observed at presentation. Treatment of CD56(+) ALL resulted in a lower rate of complete remissions (70% vs. 88%) (p=0.001) and a higher rate of resistant disease (21% vs. 8%) (p=0.004). CD56 expression had no significant influence on overall (48% vs. 59%) and disease free survival (67% vs. 57%) at three years.
CD56 is expressed on a subset of adult T-ALL with distinct immunophenotypical features and higher resistance to therapy. Most CD56(+) ALL were treated in the high-risk arm of the GMALL study protocols owing to their non-thymic phenotype. Thus after risk adapted treatment a prognostic impact of CD56 expression was not detectable.
Haematologica 01/2009; 94(2):224-9. · 6.42 Impact Factor
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ABSTRACT: We have recently identified a common ALL patient which harboured a chromosomal fusion between the TEL gene on chromosome 12 and the ABL gene on chromosome 9. We designed an RT-PCR assay to screen 186 adult ALL and 30 childhood ALL patients for this novel translocation. We were unable to identify any additional cases with a TEL/ABL fusion product.
British Journal of Haematology 03/2008; 90(1):222 - 224. · 4.94 Impact Factor
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Thomas Burmeister,
Stefan Schwartz,
Almut Taubald,
Edgar Jost,
Thomas Lipp,
Folker Schneller,
Helmut Diedrich,
Henrike Thomssen,
Ulrich J M Mey,
Jan Eucker, Harald Rieder,
Nicola Gökbuget,
Dieter Hoelzer,
Eckhard Thiel
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ABSTRACT: RT-PCR detects chimeric BCR-ABL mRNA in approximately 25% of adult acute lymphoblastic leukemia (ALL) cases. Minor breakpoint transcripts (e1a2) are found in about 70% of positive cases and major breakpoint transcripts (e13a2, e14a2) in about 30% of cases. However, other atypical transcripts are sometimes observed. We report experience gained in the GMALL Study Group and identified 8 BCR-ABL-positive adult ALL cases with such atypical transcripts: 5 with e1a3, 2 with e13a3 (b2a3), and 1 with e6a2. This corresponds to a prevalence of 1-2% of all BCR-ABL-positive cases. The clinical courses are reported and diagnostic proposals are made.
Haematologica 01/2008; 92(12):1699-702. · 6.42 Impact Factor
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ABSTRACT: The impact of cytogenetic characterization based on chromosome banding analyses and fluorescence in situ hybridization on clinical decision making has increased dramatically during recent years. Therefore, laboratory techniques have to be optimized to provide reliable results for optimal patient care. In addition, quick and correct results save time and money by preventing unnecessary additional diagnostics and suboptimal treatment approaches. It was our aim to present proposals for standardized protocols to improve the diagnosis, and hence the treatment outcome, of hematologic malignancies.
Genes Chromosomes and Cancer 06/2007; 46(5):494-9. · 3.31 Impact Factor
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ABSTRACT: The NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia (T-ALL) has recently been identified as a possible target for imatinib and related tyrosine kinase inhibitors, but exact data regarding the prognostic impact and frequency of the several putative NUP214-ABL1 mRNA transcripts are still missing. We investigated 279 adult patients with T-ALL treated within the framework of the GMALL 5/93 and 6/99 therapy trials for NUP214-ABL1 by using a novel multiplex real-time, quantitative polymerase chain reaction (PCR). Eleven (3.9%) patients were NUP214-ABL1 positive, and 5 different transcripts were observed; 8 patients had a thymic immunophenotype, 1 had an early T-cell immunophenotype, and 2 had a mature T-cell immunophenotype. NUP214-ABL1-positive and -negative patients did not differ significantly in their major clinical features. In contrast to previous reports suggesting an adverse clinical course for NUP214-ABL1-positive patients, no significant difference in overall survival was observed. Based on the results, we have established and tested a novel PCR method for simplified detection of the NUP214-ABL1 fusion gene.
Blood 12/2006; 108(10):3556-9. · 9.90 Impact Factor
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Julie Earl,
Li Yan,
Louis J Vitone,
Janet Risk,
Steve J Kemp,
Chris McFaul,
John P Neoptolemos,
William Greenhalf,
Ralf Kress,
Mercedes Sina-Frey,
Stephan A Hahn, Harald Rieder,
Detlef K Bartsch
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ABSTRACT: Familial pancreatic cancer (FPC) describes a group of families where the inheritance of pancreatic cancer is consistent with an autosomal-dominant mode of inheritance. The 4q32-34 region has been previously identified as a potential locus for FPC in a large American family.
The region was allelotyped in 231 individuals from 77 European families using nine microsatellite markers, and haplotyping was possible in 191 individuals from 41 families. Families were selected based on at least two affected first-degree relatives with no other cancer syndromes.
Linkage to most of the locus was excluded based on LOD scores less than -2.0. Eight families were excluded from linkage to 4q32-34 based on haplotypes not segregating with the disease compared with a predicted six to seven families. Two groups of families were identified, which seem to share common alleles within the minimal disease-associated region of 4q32-34, one group with an apparently earlier age of cancer death than the other pancreatic cancer families. Four genes were identified with potential tumor suppressor roles within the locus in regions that could not be excluded based on the LOD score. These were HMGB2, PPID, MORF4, and SPOCK3. DNA sequence analysis of exons of these genes in affected individuals and in pancreatic cancer cell lines did not reveal any mutations.
This locus is unlikely to harbor a FPC gene in the majority of our European families.
Cancer Epidemiology Biomarkers & Prevention 11/2006; 15(10):1948-55. · 4.12 Impact Factor
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ABSTRACT: Familial pancreatic cancer (FPC) is a rare tumour syndrome and its underlying major gene defect is still unknown. Recently, CHEK2 has been identified as multi-organ cancer susceptibility gene associated with a predisposition to breast, prostate and colon cancer. Since these cancers also are associated with some FPC families, we have analysed 35 index patients of German FPC families for CHEK2 mutations. The CHEK2 * 1100delC mutation was found in 1 (3%) of 35 FPC families. Given the low expected mutation rate of up to 1.4% for CHEK2 * 1100delC in the European population our data are suggestive for possible contribution of CHEK2 mutations to a small subset of FPC.
Familial Cancer 02/2006; 5(4):305-8. · 1.30 Impact Factor
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Beate Gleissner,
Nicola Goekbuget, Harald Rieder,
Renate Arnold,
Stefan Schwartz,
Helmut Diedrich,
Claudia Schoch,
Barbara Heinze,
Christa Fonatsch,
Claus R Bartram,
Dieter Hoelzer,
Eckhard Thiel
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ABSTRACT: Immunophenotyping disclosed CD10 negativity in 70 of 2408 cases of B-lineage acute lymphoblastic leukemia (ALL), although other criteria followed classification of pre-B ALL (eg, cytoplasmic immunoglobulin positivity). These blasts showed high myeloid antigen expression (60% CD65 positivity) and reacted with antibody 7.1 in 95% of the cases. MLL-AF4 fusion transcripts or an 11q23/MLL rearrangement or both were evident in 46 of 56 samples (82%). Although 83% of the patients achieved complete remission, the remission duration remained remarkably low: 141 days for MLL rearrangement-positive and 245 days for MLL rearrangement-negative CD10(-) pre-B ALL. Thus, the overall survival probability 3 years after diagnosis was 0.34 +/- 0.20 SE in MLL-rearrangement-negative versus 0.12 +/- 0.06 SE in MLL rearrangement-positive CD10- pre-B ALL. Our data identify CD10- cytoplasmic immunoglobulin-positive pre-B ALL as a rare (2.2%) but distinct immuno-subtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome.
Blood 01/2006; 106(13):4054-6. · 9.90 Impact Factor
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ABSTRACT: The RNASEL (encoding ribonuclease L) gene Glu265X mutation has been implicated in familial prostate cancer, and an association between the RNASEL Arg462Gln variant and sporadic and familial prostate cancer, has also been suggested. Because prostate cancer occurs in some familial pancreatic cancer families, we evaluated the role of the RNASEL gene variants Glu265X and Arg462Gln in the etiology of pancreatic cancer. Exon 2 of the RNASEL gene was directly sequenced in the germline of 36 familial and 75 sporadic pancreatic cancer patients and in 108 controls. The Glu265X mutation was identified in one (2.8%) familial and one (1.3%) sporadic pancreatic cancer case, but not in any of the controls. Arg462Gln variants were identified in 61 (56%) controls and in 55 (73%) sporadic pancreatic cancer cases with 8 (7%) and 12 (16%) homozygotes, respectively (p = 0.009). For homozygous carriers the increased risk for pancreatic cancer was 3.5 (odds ratio [OR] = 3.53, 95% confidence interval [CI] = 1.11-11.46, p = 0.03). The population attributable fraction (PAF) was 38.7% (95% CI = 0.08-0.80). In familial pancreatic cancer no association between Arg462Gln genotypes and pancreatic cancer risk was evident. In sporadic pancreatic cancer there were no significant differences between Arg462Gln genotypes regarding clinical characteristics. In familial pancreatic cancer, however, patients with Arg462Gln variants had more aggressive tumors with more high grade cancers (OR = 15.40, p = 0.009) and more distant metastases (OR = 7.00, p = 0.04) than patients with the wild-type genotype. Our results suggest that RNASEL variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer, which has to be proven in large scale studies.
International Journal of Cancer 01/2006; 117(5):718-22. · 5.44 Impact Factor
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ABSTRACT: For statistical analyses in cancer cytogenetics, the genomic changes encoded by the karyotype must be translated into numerical codes. We developed a program, which extracts chromosomal gains and losses as well as breakpoints from the karyotype. The changes are compiled in tables according to the chromosome bands involved and/or depicted in projection to the respective chromosome ideogram. The data are ready to be integrated into further statistical analyses. The program may be run as desktop or Internet application.
Bioinformatics 05/2005; 21(7):1282-3. · 5.47 Impact Factor
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Robert Grützmann,
Christopher McFaul,
Detlef K Bartsch,
Mercedes Sina-Frey, Harald Rieder,
Rainer Koch,
Emma McCarthy,
William Greenhalf,
John P Neoptolemos,
Hans Detlev Saeger,
Christian Pilarsky
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ABSTRACT: Familial pancreatic cancer (FPC) (approximately 3% of all cases) has not been linked to defects in any specific gene. Germline inactivation of the gene LKB1/STK11 have been shown to cause Peutz-Jeghers syndrome (PJS) associated with a approximately 100-fold higher risk for the development of pancreatic cancer. We have analysed 39 index patients from European FPC families for mutations of LKB1/STK11 by sequencing of their DNA. No germline mutation was found within the complete coding region. Therefore, our results indicate that LKB1/STK11 is not altered in the germline of patients with hereditary pancreatic cancer.
Cancer Letters 11/2004; 214(1):63-8. · 4.24 Impact Factor
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Detlef K Bartsch,
Ralf Kress,
Mercedes Sina-Frey,
Robert Grützmann,
Berthold Gerdes,
Christian Pilarsky,
Joachim W Heise,
Klaus-Martin Schulte,
Mario Colombo-Benkmann,
Cristina Schleicher, [......],
Karl Breitschaft,
Klaus Prenzel,
Helmut Messmann,
Esther Endlicher,
Margarete Schneider,
Andreas Ziegler,
Wolff Schmiegel,
Helmut Schäfer,
Matthias Rothmund, Harald Rieder
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ABSTRACT: Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9-3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.
International Journal of Cancer 08/2004; 110(6):902-6. · 5.44 Impact Factor
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ABSTRACT: The dismal prognosis of ductal pancreatic adenocarcinoma is mainly attributable to advanced tumor stages at the time of diagnosis. Meanwhile, familial pancreatic cancer is an established hereditary tumor entity that is responsible for approximately 3% of pancreatic cancer (PC) cases. Therefore, analysis of the family history may help to identify individuals at increased risk of developing PC. These include members of families with a history of PC as well as those of families with distinct hereditary cancer syndromes such as Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma syndrome, hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer. In future, the identification of germline mutations in genes predisposing to PC, together with the analysis of exogenous risk factors, could be used for a more precise risk assessment for the development of PC. This may allow the application of invasive screening methods for the identification of early PC or, even better, its precursor lesions in high-risk individuals, providing the option of timely curative pancreatectomy.
Familial Cancer 02/2004; 3(1):69-74. · 1.30 Impact Factor
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Barbara Wassmann,
Heike Pfeifer,
Urban J Scheuring,
Anja Binckebanck,
Nicola Gökbuget,
Johannes Atta,
Patrick Brück, Harald Rieder,
Claudia Schoch,
Lothar Leimer,
Rainer Schwerdtfeger,
Gerhard Ehninger,
Thomas Lipp,
Jolanta Perz,
Matthias Stelljes,
Harald Gschaidmeier,
Dieter Hoelzer,
Oliver G Ottmann
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ABSTRACT: Imatinib has pronounced but brief antileukemic activity in advanced Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). We assessed the prognostic impact of pretreatment disease features and the early bone marrow (BM) response in 68 consecutive patients with Ph(+)ALL receiving imatinib salvage therapy. A complete hematologic or marrow response was achieved by 92% of patients with BM blasts below 5% on day 14, whereas 62.5% of patients with more than 5% BM blasts on day 14 were nonresponders. Similarly, time to progression (TTP) was superior in patients with a good day 14 response (5.2 versus 0.9 months; P <.0001). Prior complete remission of less than 6 months, white blood cell count of more than 10 x 10(9)/L, circulating peripheral blood blasts at diagnosis, additional Philadelphia chromosomes, or at least 2 Bcr-Abl fusion signals were associated with significantly inferior remission rate and response duration. In patients without poor prognostic features, single-agent imatinib may be appropriate before transplant salvage therapy. Conversely, patients with clinically or cytogenetically defined poor-risk features are candidates for trials of upfront imatinib in combination with other agents.
Blood 02/2004; 103(4):1495-8. · 9.90 Impact Factor
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Hereditary Cancer in Clinical Practice 01/2004; 2(3):149-50. · 1.68 Impact Factor
