No Adverse Impact of 13q14 and P53 Deletion, t(4;14)(p16;q32) or Overrepresentation of CMYC(8q24) as Detected by Fluorescence In Situ Hybridization on Outcome in Patients with Multiple Myeloma Following Dose-Reduced Allogeneic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5038-5038
Author(s):  
Timon Hansen ◽  
Georgia Schilling ◽  
Peter Liebisch ◽  
Rainer Schwerdtfeger ◽  
Jose Antonio Perez-Simon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chromosomal Abnormalities ◽  
Genetic Changes ◽  
Significant Difference ◽  
Study Population

Abstract Deletions of chromosome bands 13q14 and 17p13 (P53) as well as t(4;14)(p16;q32) or overrepresentation of CMYC are known to be adverse prognostic factors for time to progression (TTP) and overall survival (OS) in myeloma patients receiving conventional or high-dose chemotherapy followed by autologous stem cell transplantation. We investigated the impact of these chromosomal abnormalities as detected by fluorescence in situ hybridization combined with immunofluorescent cytoplasm immunoglobulin staining (cIg-FISH) on outcome after dose-reduced melphalan/fludarabin based allogeneic stem cell transplantation (SCT) in 64 patients (pts) with multiple myeloma (MM). Median age was 52 years (34 – 67 ys.), 38 patients were male, 26 female. 45 pts received stem cell graft from an unrelated donor and 19 pts from HLA-identical sibling. Deletion of 13q14 was found in 35 out of 64 pts (55%), P53 deletion in 7 out of 64 pts (11%), t(4;14)(p16;q32) in 11 out of 56 pts (20%) and trisomy of CMYC in 12 out of 55 pts (22%). The following strong correlations among the genetic changes have been seen: six out of seven pts with P53 deletion also showed deletion in chromosome band 13q14 (86%), which was also found in nine out of eleven pts with t(4;14) (82% del 13) and nine out of twelve pts with CMYC trisomy (75% del 13). The estimated event-free (EFS) and overall survival (OS) at four years for the entire study population was 48% and 57%, respectively. No significant difference of the estimated event-free survival at 3 years was seen for pts with del 13 (42% vs 54%, p=0,4), with P53 deletion (43% vs 49%, p=0,27) and for pts with t(4;14) (46% vs 62%, p=0,69) or CMYC overrepresentation (37% vs 50%, p=0,35). Comparison of pts showing both del 13 and P53 deletion, del 13 and t(4;14), del 13 and trisomy of CMYC or t(4;14) and CMYC trisomy with the rest of the study population did not show a significantly reduced EFS either. Even the comparison of pts with any chromosomal abnormalities and pts without any genetic changes detected by FISH did not show a significant difference in EFS (48% vs 50%, p=0,8). These preliminary data suggest that the negative prognostic impact of chromosomal abnormalities such as deletion of 13q14, P53 deletion, t(4;14) and overrepresentation of CMYC may be overcome by allogeneic SCT probably due to the graft versus myeloma effect.

P53 Gene Deletion Detected by Fluorescence In Situ Hybridization Is an Adverse Prognostic Factor for Patients with Multiple Myeloma Following Autologous Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4884-4884
Author(s):  
Xiao Ying Qi ◽  
Qi Long Yi ◽  
Donna Reece ◽  
A. Keith Stewart ◽  
Hong Chang
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
P53 Gene ◽  
High Dose Chemotherapy ◽  
High Dose

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.

p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following 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
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
P53 Gene ◽  
High Dose Chemotherapy ◽  
High Dose

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)

Deletion of p53 as Detected by Fluorescence In Situ Hybridization Is Associated with Significant Shorter Event-Free Survival in Patients with Multiple Myeloma Who Are Receiving Allogeneic Blood Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4338-4338
Author(s):  
Georgia Schilling ◽  
Timon Hansen ◽  
Jose Antonio Perez-Simon ◽  
Rainer Schwerdtfeger ◽  
Martin Bornhaeuser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
In Situ Hybridization ◽  
Stem Cell Transplantation ◽  
Fluorescence In Situ Hybridization ◽  
Cell Transplantation ◽  
Chromosome Band ◽  
Blood Stem Cell Transplantation

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.

scholarly journals FIFTEEN YEARS OF SINGLE CENTER EXPERIENCE WITH STEM CELL TRANSPLANTATION FOR MULTIPLE MYELOMA: A RETROSPECTIVE ANALYSIS

2013 ◽  
Vol 56 (1) ◽  
pp. 9-13
Author(s):  
Jakub Radocha ◽  
Vladimír Maisnar ◽  
Alžběta Zavřelová ◽  
Melanie Cermanová ◽  
Miriam Lánská ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Renal Impairment ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
New Drugs ◽  
Long Term Outcome ◽  
Free Survival ◽  
Significant Difference

Introduction: Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department. Patients and methods: We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant. Results: Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome. Conclusion: Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.

scholarly journals Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

2021 ◽  
Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Relapse Group

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

scholarly journals Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma

2019 ◽  
Vol 37 (19) ◽  
pp. 1617-1628 ◽  
Author(s):  
Sam H. Ahmedzai ◽  
John A. Snowden ◽  
Andrew John Ashcroft ◽  
David Allan Cairns ◽  
Cathy Williams ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Adverse Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Random Assignment ◽  
Time To Progression ◽  
Patient Reported

PURPOSE Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment ( P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment ( P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4548-4548
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Maialen Lasa ◽  
Osman Ahmed ◽  
Marco Bua ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

NON-Cryopreserved Hematopoietic STEM CELL Transplantation in Multiple Myeloma. a Single Center Experience in Oran (ALGERIA)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1990-1990
Author(s):  
Amine MA Bekadja ◽  
Souad ST Talhi ◽  
Hafida OH Ouldjeriouat ◽  
Osmani OS Soufi ◽  
Mohamed BM Brahimi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem

Abstract Introduction: For younger patients under 65 years of age, induction followed by high-dose chemotherapy with autologous stem cell transplantation (ASCT) is the standard treatment in multiple myeloma (MM). There is limited experience with non-cryopreserved autologous hematopoietic stem cell transplantation. We evaluated the efficacy and safety of non-cryopreserved storage of ASCT in patients undergoing ASCT for MM. Patients and methods: Autologous stem cell was mobilized using G-CSF alone (10 µg/kg/day for 5 days). Leukapheresis to harvest stem cells were performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at +4°C until reinfusion on day 0. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients. Results: From May 2009 to December 2013, 134 patients with MM were treated in our center in Oran. The median age at ASCT was 55 years (range; 27-67). There were 80 males and 54 females. The median harvested CD34+ cell count was 3,5x106/kg (range; 1, 22 to 13, 24). All patients had engraftment on the median of day 10 (range; 7 to 17) and platelet transfusion independence on the median of day 13 (range; 9 to 24). There was no graft failure. Mucositis grade 3/4 was seen in 68% patients. Transplant related mortality at 100 days was 2.9%. The overall response to transplant was 92%. In the 130 evaluable patients, the median post-transplant overall survival had not been reached. The estimated overall survival at 75 months was 63% with 95% confidence interval and the median post-transplant disease free Survival was 35 months (0.05%). 93 (72%) patients are alive and 75 (81%) without disease activity after a median follow-up of 35 months (range; 3 to 75). Discussion: We conclude that high dose chemotherapy and autologous transplant with non cryopreserved ASCT is a simple, effective and safe method for MM with equivalent results, and that cryopreservation is not necessary in the treatment of MM under our work conditions in developing countries Disclosures No relevant conflicts of interest to declare.

scholarly journals Pre-engraftment clinically significant CMV infection after allogeneic hematopoietic stem cell transplantation and its impact on engraftment

2021 ◽  
Author(s):  
Marcia Garnica ◽  
Sylvia Dalcolmo ◽  
Bianca Gaio ◽  
Andreia Almeida ◽  
Juliana Rivello ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Importance ◽  
Close Monitoring ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Clinically Significant ◽  
Few Data

Abstract Pre-engraftment cytomegalovirus infection (CMVi) is a challenge in patients receiving allogeneic stem cell transplantation (Allo-HCT), as few data have been reported on its clinical importance. This study describes the clinical outcomes of pre-engraftment CMVi and compares them with those of episodes developing after engraftment in HCT patients. We performed a retrospective study of patients who underwent Allo-HCT from 2016 to 2020, including 111 recipients monitored by real-time PCR assay. Clinically significant CMVi (csCMVi) was documented in 81 (73%) patients. There were 29 (26%) cases of pre-engraftment csCMVi. No significant difference was observed regarding virological features, but patients with pre-engraftment csCMVi had a delayed start in treatment (24 vs. 12 days, p < 0.001) compared with those with postengraftment events. Pre-engraftment csCMVi was associated with a delay in engraftment (20 vs. 16 days, p = 0.02) and worse overall survival (54% vs. 73% 1-year OS; p = 0.020) than postengraftment events. In conclusion, pre-engraftment csCMVi occurred in 26% of our patients and was associated with engraftment delay and worse overall survival. Close monitoring of CMV DNAemia is necessary to identify these patients earlier. Prospective studies, including patients with letermovir prophylaxis, are necessary to define the standard in the management and care of this population.

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