Deletion of chromosome band 13q14 as detected by fluorescence in situ hybridization is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4056-4061 ◽  
Author(s):  
N. Kroger
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4338-4338
Author(s):  
Georgia Schilling ◽  
Timon Hansen ◽  
Jose Antonio Perez-Simon ◽  
Rainer Schwerdtfeger ◽  
Martin Bornhaeuser ◽  
...  

Abstract Deletion of chromosome band 17p13 (P53) is known to be an adverse prognostic factor for time to progression (TTP) and overall survival (OS) in myeloma patients receiving conventional or high-dose chemotherapy. In this retrospective multicenter study, we investigated the impact of P53 deletion as detected by fluorescence in situ hybridization combined with immunofluorescent cytoplasm immunoglobulin staining (cIg-FISH) on outcome after allogeneic blood stem cell transplantation (SCT) in 50 patients (pts) with advanced or relapsed multiple myeloma (MM). Median age was 51 years (34 – 67 ys.), 32 patients were male, 18 female. Thirty pts received a stem cell graft from an unrelated donor, and 20 pts from a HLA-identical sibling. P53 gene deletion was found in 5 out of 49 pts (10,2 %). Deletion 13 detected by cIg-FISH was found in 20 out of 47 pts (42%). There was a strong correlation between P53 deletion and deletion 13: four out of the five patients with P53 deletion also showed deletion in chromosome band 13q14. The estimated event-free (EFS) and overall survival (OS) at three years for the entire study population was 43% and 65%, respectively. For patients with del 13 only a trend for a worse 3 year EFS was seen (38% vs 42%, p=0.2), while pts with P53 deletion had a significant reduced EFS (0% vs 46%, p=0.0001). Three out of five pts with P53 deletion relapsed very early after allogeneic SCT (day 81, 108 and 287 respectively). These data suggest that P53 is a risk factor for patients with MM treated with allogeneic SCT which can not be overcome by this treatment strategy.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5214-5214
Author(s):  
Huiying Qiu ◽  
Yongquan Xue ◽  
Jinlan Jin ◽  
De Pei Wu

Abstract Objective Monitoring of minimal residual disease (MRD) and cellular chimerism in patients with hematopoietic malignancies after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods From May 2001 to June 2005, seventy four patients were received allo-HSCT. Including 50 Males and 24 females. 41 patients received sibling HLA-matched BMT, 7 patients received un-related BMT, 9 patients received Nonmyeloablative stem cell transplantation (NST), 14 patients received related haploidentical transplantation and 3 patients received allo-PBSCT. Among them, 45 patients were diagnosed with CML, 13 patients with AML, 14 patients with ALL, one patient with Multiple myeloma and one patient with malignant lymphoma. Chimerism and MRD were monitored using X and Y specific centromeric probes or gene probes for BCR/ABL, MLL and AML1/ETO by fluorescence in situ hybridization (FISH),1000 cells were analysised. Results Among 18 patients, received sex-matched transplant, we did not found the former chromosome rearrangements in 14 patients after transplantation, MRD were detected in 17% and 10% of cells in two patients, MRD were decreased from 10% to 1% of cells after the reduction of the dose of immunotherapy in one patient four month later, the patient was still in remission one year after transplantation. Another patient died of sever GVHD after the reduction of immunotherapy. 2 patients were found to have the former chromosomal rearrangement 1 and 4 month after transplantation respectively who did not achieve remission after chemotherapy and died 3 and 5 months respectively after transplantation. Over 99% donor chimerisms were found in 44 patients on day 25, donor cells were at a low level (96.2%~98.7) in 7 patients on day 25, and increased over 99% on day 180, they were in remission without relapse. The donor chimerisms decreased gradually in 6 patients, host cells were found over 20 cells, 3 patients showed cytogenetic or hematologic bone marrow relapse, two patients died of sever GVHD after the reduction of cyclosporine A, Over 99% donor chimerisms was achieved in one patient. Conclusion FISH could play a pivotal role in the detection of MRD and chimerism. It is helpful to the evaluation of graft and relapse, to the guide of implement of early immunotherapy.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4884-4884
Author(s):  
Xiao Ying Qi ◽  
Qi Long Yi ◽  
Donna Reece ◽  
A. Keith Stewart ◽  
Hong Chang

Abstract We investigated the relevance of p53 deletions to the clinical outcome of multiple myeloma (MM) patients treated with high-dose chemotherapy and autologous stem cell transplantation. Hemizygous p53 gene deletions were detected by cytoplasmic Ig-enhanced interphase fluorescence in situ hybridization (cIg-FISH) in 10 of 105 (9.5%) patients studied. p53 deletions were associated with higher serum calcium (p=0.0062) and creatinine (p=0.013) levels but there were no association with patient age, gender, β-2 microglobulin, C-reactive protein, hemoglobin, albumin, bone lytic lesions, or immunoglobulin isotype. There were no association of p53 deletions with chromosome 13q deletions, translocation t(11;14) or t(4;14). The overall response rates were similar in patients with and without p53 deletions (67% vs 71%). However, patients with p53 deletions had significantly shorter progression free (median 7.9 vs. 25.7 months, p=0.0324) and overall survival (median 14.7 vs. 48.1 months, p=0.0008) than patients without a p53 deletion. A multivariate analysis confirmed p53 deletion was an independent prognostic factor predicting shortened progression free (p=0.0009) or overall survival (p=0.0002) in myeloma patients after high-dose chemotherapy and autologous stem cell transplantation.


Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 358-360 ◽  
Author(s):  
Hong Chang ◽  
Connie Qi ◽  
Qi-Long Yi ◽  
Donna Reece ◽  
A. Keith Stewart

Abstract We investigated the relevance of p53 deletions to the clinical outcome of patients with multiple myeloma (MM) treated with high-dose chemotherapy and autologous stem cell transplantation. Hemizygous p53 gene deletions were detected by fluorescence in situ hybridization in 10 of 105 (9.5%) patients studied. p53 deletions were associated with higher serum calcium (P = .0062) and creatinine (P = .013) levels, but there were no association with patient age, gender, β2-microglobulin, C-reactive protein, hemoglobin, albumin or bone lytic lesions, or immunoglobulin isotype. There were no associations of p53 deletions with 13q deletions or translocations t(11;14) or t(4;14). Patients with p53 deletions had significantly shorter progression-free (median, 7.9 versus 25.7 months, P = .0324) and overall survival (median, 14.7 versus 48.1 months, P = .0008) than patients without a p53 deletion. A multivariate analysis confirmed p53 deletion was an independent prognostic factor predicting shortened progression-free (P = .0009) or overall survival (P = .0002) in patients with MM after high-dose chemotherapy and autologous stem cell transplantation. (Blood. 2005;105:358-360)


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