XRCC1‐mediated DNA repair is associated with progression‐free survival of multiple myeloma patients after autologous stem cell transplant

2019 ◽  
Vol 58 (12) ◽  
pp. 2327-2339
Author(s):  
Avinash K. Persaud ◽  
Junan Li ◽  
Jasmine A. Johnson ◽  
Nathan Seligson ◽  
Douglas W. Sborov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dna Repair ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

Salvage Tandem Autologous Stem Cell Transplant with Consolidation for Relapsed Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5497-5497
Author(s):  
Kamal Kant Singh Abbi ◽  
Sonya Behrends ◽  
Margarida Silverman ◽  
Umar Farooq ◽  
Kalyan Nadiminti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Progressive Disease ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Free Survival

Abstract Background: Therapeutic options for patients with Multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (SCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second SCT, with no clear standard of care. Upfront tandem transplantation has been shown to improve both progression free survival and overall survival. But currently, there is little data regarding the application of tandem SCT in relapsed multiple myeloma patients. Methods: We retrospectively analyzed the outcomes of patients who underwent salvage melphalan-based tandem SCT for relapsed MM at University of Iowa Hospitals and clinics. Progression free survival (PFS) was defined as the time from date of the first salvage SCT to disease progression or death, whereas overall survival (OS) was defined from the date of the first salvage SCT to the date of death from any cause. Results: Between 2012 and 2015, 12 patients with MM received tandem autograft (total 24 transplants) for relapsed disease at our center. Conditioning was with VDT-melphalan 200mg/m2 (21/24), VDT-MEL 140mg/m2 (2/24) and Velcade, gemcitabine, BCNU, melphalan and dexamethasone (1/24). The median age at the salvage SCT was 48 years (range 37-58); 7 patients were female. 17% had high risk cytogenetics (including t(4;14), +1q, p53 loss) at the time of salvage SCT. Median time between previous transplant and progression of disease was 34 months (range 8-108). Of the 7 patients, who received re-induction therapy, 71% had chemotherapy refractory disease prior to salvage SCT. Response was assessed at 2-3 months post-SCT. Overall response rate was 92%. 7/12 (58%) patients achieved stringent complete remission, one patient achieved CR, one patient achieved near CR, 2/12 patients achieved VGPR and 1/12 had stable disease (SD). Following salvage tandem SCT, all patients received consolidation therapy with three drug combination, intended to be given for two years. Three patients have shown progressive disease at the time of analysis. The median PFS was 390 days (range 265- 1085) (Table-1); the median OS was 517 days (range 338-1085) (Table-2). Rate of progression free survival in the 10 evaluable patients at one year was 80%. There was no transplant related mortality. One patient died of progressive disease. Conclusions: Salvage tandem SCT is an effective strategy for relapsed MM and is especially effective in patients who had received less intensive therapy initially (single transplant and no maintenance therapy). Incorporation of novel agents (monoclonal antibodies and high doses of carfilzomib) into maintenance strategies may further improve outcomes. Figure 1. Progression free survival for all the patients Figure 1. Progression free survival for all the patients Figure 2. Overall survival for all the patients Figure 2. Overall survival for all the patients Disclosures Farooq: Kite Pharma: Research Funding.

Weekly Cyclophosphamide and Alternate Day Prednisone: An Effective, Convenient and Well Tolerated Treatment for Relapsed Multiple Myeloma Following Autologous Stem Cell Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4917-4917
Author(s):  
A. Keith Stewart ◽  
Young Trieu ◽  
Suzanne Trudel ◽  
Greg Pond ◽  
Joseph Mikhael ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Alkylating Agents ◽  
Progression Free Survival ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Protein Reduction

Abstract Alkylating agents remain among the most potent therapies available for treatment of Multiple Myeloma (MM). Their use prior to, or following, autologous stem cell transplant (ASCT) is, however, compromised by concerns about stem cell quality and by myelosuppression limiting effective dose delivered. To address this concern we have studied a combination of cyclophosphamide 500 mg p.o. once weekly and prednisone 100 mg p.o. on alternate days in 66 patients requiring salvage therapy post-ASCT. Dose reductions were allowed for toxicity beginning at cycle 2. On an intent to treat basis, 66 patients received this regimen, however, 7 of these patients were not fully evaluable for response due to non-secretory disease. Of the 59 patients evaluable for response, the median time from transplant to treatment was 26.4 months (range, 6.0 to 66.6). The median time from post-transplant relapse to start of cyclophosphamide and prednisone (C/P) therapy was 1.4 months. The median number of therapies from time of diagnosis to C/P initiation was 2 (range, 1.0 to 5.0). At the date of analysis, treatment with C/P is ongoing in 12 (20.3%) patients, with a median duration of 3.6 months (range, 1.9 to 11.6). The 47 patients who have completed C/P therapy were treated for a median time of 5.5 months (range, 0.5 to 21.7). The reason for discontinuation among these 47 patients included disease progression (42.6% of patients discontinued), plateau disease (21.3%), receiving a second transplant (17.0%), toxicity (10.6%), or switched to another regimen (8.5%). A partial response (>50% protein reduction) was obtained in 37.3% of patients, 18.6% attained minimal response (25–50% protein reduction), 33.8% patients stable disease, while 10.2% patients had progressed on treatment. The estimated median (95% CI) months of progression-free survival after start of C/P treatment is 14.9 (8.7, 21.7). Twenty-three (38.9%) of patients have relapsed after C/P treatment, a median (range) of 8.7 (0.5–65.7) months after start of C/P treatment. At 6 months 74.3% (95% C.I. 61.9% – 89.1%) of patients were progression-free with 28% (95% CI: 16.1–49.2%) progression free at two years. At time of analysis, 44 (74.6%) patients are still alive, with a median follow up of 10.6 months (range, 1.2 to 65.7) since the start of C/P therapy. Fifteen patients have died at a median 13.0 months (range, 1.4 to 61.7) since the time of C/P initiation. The median overall survival (95% C.I.) is estimated to be 35.9 months (24.2, NA). These results demonstrate that the combination of oral cyclophosphamide and prednisone is an effective (56% MR or PR), very well tolerated (10% discontinued due to toxicity) and convenient treatment as salvage MM therapy post-ASCT. The relative lack of myelosuppression allows for re-collection of stem cells and salvage transplant while retaining other active second line agents for later relapse. This regimen thus compares favorably with recent salvage therapeutics introduced in MM and is now being studied in combination with these newer active agents and in induction therapy.

Autologous stem cell transplantation versus no transplant in patients above 70 with multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20509-e20509
Author(s):  
Christopher Lemieux ◽  
Lori S. Muffly ◽  
David Joseph Iberri ◽  
Andrew Rezvani ◽  
Robert Lowsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival ◽  
First Line Therapy ◽  
Included Patient

e20509 Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m2 (75%, n = 40) and 140 mg/m2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients < 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]

Short Progression Free Survival Post Non-Myeloablative Sibling Allogeneic Stem Cell Transplantion for Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4323-4323
Author(s):  
Kevin Song ◽  
Heather J. Sutherland ◽  
John D. Shepherd ◽  
Yasser Abou Mourad ◽  
Michael J Barnett ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Free Survival ◽  
Graft Versus Host

Abstract 4323 Introduction Allogeneic stem cell transplant has been considered the only potentially curative treatment for patients with myeloma. Due to the high treatment related mortality associated with myeloablative allogeneic stem cell transplantation, non-myeloablative allogeneic stem cell transplantion is being investigated. Methods Between May 2003 and June 2008, 23 patients received a non-myeloablative allogeneic stem cell transplant (NMT) using a fully matched sibling as the donor. All had received a previous autologous stem cell transplant (ASCT). 17 received the NMT as a part of a planned tandem transplant post ASCT. Six received the NMT after relapse post ASCT. Conditioning chemotherapy was a combination of cyclophosphamide 1000 mg/m2 daily x 2 days and Fludarabine 25mg/m2 daily for 5 days. Survival was measured from the date of allogeneic stem cell infusion. Results Median age at NMT was 52 years. Eight were female. Immunoglobulin isotype was 13 IgG; 5 IgA; 1 IgD; 4 light chain. ISS stage was 10 – stage 1; 8 – stage 2; 3- stage 3; 2 – insufficient information. 9/21 had del 13q; 3/9 t (4;14); 1/7 del 17p. Disease status at the time of NMT were 5 CR/nCR, 11 PR, 1 SD, 3 relapse chemo-sensitive, 3 relapse chemo-resistant. Median follow-up is 29 months (7 – 65 months). Median event free survival (EFS) for all patients is 17 months (95 % CI 8-26 months). Median EFS for the 17 patients who received NMT as a part of a planned tandem procedure was 18 months. Median overall survival (OS) for all patients is 29 months (95% CI unable to calculate). At the time of analysis 17 patients remain alive. Five patients are alive in continuous remission at a median of 40.9 months from NMT (13.5-47.6 months). Twelve patients have active disease requiring treatment. Three patients have died of myeloma, one of graft-versus-host-disease (GVHD) and two of other causes. Nineteen patients (83%) developed GVHD at some time post-transplant. Of 14 patients who have relapsed, eleven patients had GVHD at the time of relapse. Of the 6 patient who received the NMT after relapse post ASCT, 5 have relapsed post NMT and one died of GVHD within 9 months. Conclusion Non-myeloablative sibling allogeneic stem cell transplantation for myeloma produces short progression free survival in-spite of the presence of graft-versus-host-disease and only a limited number of patients benefit. Patient who receive this treatment after relapse from prior autologous stem cell transplant do particularly poorly. Improved overall survival is primary due to improvements in post-relapse myeloma therapy.

Progression-free survival at 24 months as a landmark after autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7522-7522
Author(s):  
Aung M. Tun ◽  
Seth Maliske ◽  
Yucai Wang ◽  
Matthew J. Maurer ◽  
Ivana N. M. Micallef ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

7522 Background: Patients with newly diagnoseddiffuse large B-cell lymphoma (DLBCL) who achieve event-free survival at 24 months (EFS24) following immunochemotherapy (IC) have excellent overall survival (OS) similar to that of age- and sex-matched general population. The standard of care for patients with relapsed or refractory (RR) DLBCL following frontline IC is salvage therapy followed by autologous stem cell transplant (ASCT). The goal of this study is to evaluate the role of progression-free survival (PFS) at 24 months (PFS24) as a landmark after ASCT in patients with RR DLBCL. Methods: Patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Post-ASCT PFS, OS, and post-relapse survival (PRS) were plotted by Kaplan-Meier method, and cumulative incidences of relapse vs non-relapse mortality (NRM) and different causes of death were compared accounting for competing events. Statistical analyses were performed in EZR v1.54. Results: A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow up of 8.0 years (95% CI 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, post-ASCT relapse rate was much higher than NRM rate (48.1 vs 9.1% at 5-year). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and NRM were similar (14.8% and 12.3% at 5-year). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma related and unrelated death rates were similar after achieving PFS24 (Table). For all patients who had a post-ASCT relapse, median PRS was 0.7 years (95% CI 0.5-0.9), and late relapse ( > 2 vs ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] vs 0.5 [0.3-0.7] years, p < 0.001). Conclusions: Post-ASCT PFS24 is an important prognostic predictor of post-ASCT outcomes in patients with RR DLBCL following frontline IC.[Table: see text]

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