scholarly journals High-Dose Chemotherapy Followed by Peripheral and/or Bone Marrow Stem Cell Transplant in Patients With Advanced Sarcoma: Experience of a Canadian Centre

Sarcoma ◽  
2004 ◽  
Vol 8 (2-3) ◽  
pp. 63-69 ◽  
Author(s):  
Sébastien J. Hotte ◽  
Anne M. Smith ◽  
Vivien H.C. Bramwell ◽  
Kang Howson-Jan

Purpose: Few reports have been published on the evaluation of stem cell auto transplantation for chemosensitive sarcomas. Some suggest benefit, others do not. We present results of 24 patients with sarcoma undergoing autotransplantation at a Canadian institution.Patients and Methods: Twenty-four patients were treated between 1988 and 1998: 23 were ≥18 years (median 27; range 12–56); genders were equal; 12 patients had Ewing's sarcoma. At diagnosis, 12 (50%) had metastatic disease. Prior to autotransplant, all had ≥1 chemotherapy regimen. Fourteen (58%) were in complete remission (CR) and seven (29%) had minimal residual disease. All received etoposide 60 mg/kg (Day –4), melphalan 140 mg/m2on (Day –3) and a stem cell reinfusion (Day 0).Results: Three patients (12.5%) were alive and disease-free with median follow-up of 92 months (80–142); one was alive with disease 32 months post-autotransplant. Twenty had died (disease, 17; transplant-related, 2; unknown, 1). Of the four alive, three had Ewing's sarcoma, one alveolar rhabdomyosarcoma, and all were in CR at transplant. Median time to relapse was 6 months (2–59). Sixteen of 18 (89%) relapsed within 1 year. Median overall survival was 10 months (0–137). A trend towards improved survival (P=0.07) was evident for patients in CR prior to autotransplant.Conclusions: Stem cell autotransplantation does not benefit most patients with sarcoma. A subgroup of high-risk patients in CR may fare better and warrant further study.

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9004-9004
Author(s):  
A. Tienghi ◽  
S. Ferrari ◽  
M. Mercuri ◽  
P. Giovanis ◽  
E. Barbieri ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10545-10545
Author(s):  
E. Palmerini ◽  
A. Brach Del Prever ◽  
F. Fagioli ◽  
R. Luksch ◽  
A. Prete ◽  
...  

10545 Background: Nearly 30–40% of patients with newly diagnosed, non-metastatic Ewing's Sarcoma (EWS) relapse. Post-relapse survival (PRS) in EWS is very poor, with less than 15–20% alive 5-years after recurrence. The role of high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is under investigation in metastatic and high risk localized EWS patients. In order to improve PRS, we employed HDCT with ASCT in EWS patients at 1st relapse. Methods: All non-metastatic EWS patients treated in Italian Sarcoma Group centers who relapsed between 1999 and June 2008 were offered HDCT (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m2) with ASCT whenever possible (no previous HDCT; stable or responding disease after standard dose chemotherapy; adequate peripheral blood stem cells harvest). Results: 72 EWS patients experienced disease recurrence. Fifty (62%) were male. Twenty-eight (39%) of patients had previously received HDCT. Median relapse free interval (RFI) was 16 months (2.8–64). Pattern of relapse was: lung metastases in 20 (28%) patients, bone metastases in 12 (16%), local recurrence in 11 (15%) and multiple sites in 29 (40%). Treatment at 1st relapse was: standard dose chemotherapy in 31 (43%) patients; HDCT followed by ASCT in 24 (33%); palliative treatment in 12 (17%) and surgery only in 5 (7%). Three patients died of treatment-related toxicity. With a median follow-up of 24 months (1–64), the 3-year post-relapse survival (PRS) was 21% (95%CI 7–35). 3-year PRS was better for patients with a lung only relapse [48%, (95%CI 21–74)] and a RFI > 2 years [51%, (95%CI 27–76)]. 3-year PRS was 33% (95%CI 13–54) for patients treated with HDCT and 22% (95%CI 6–39) for those receiving standard dose chemotherapy. A significant (P 0.02) advantage was observed in the subgroup of patients with a shorter RFI treated with HDCT [3-year PRS 29% (95%CI 5–52)] compared to those treated with standard dose chemotherapy [3-years PRS 13%, (95%CI 2–29)]. Conclusions: Pattern of recurrence and RFI are the main factors influencing PRS in EWS. The use of HDCT with ASCT in recurrent EWS is investigational. Patients with shorter RFI could more likely benefit from HDCT. No significant financial relationships to disclose.


2014 ◽  
Vol 55 (10) ◽  
pp. 2319-2327 ◽  
Author(s):  
Yngvild N. Blaker ◽  
Marianne B. Eide ◽  
Knut Liestøl ◽  
Grete F. Lauritzsen ◽  
Arne Kolstad ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5325-5325
Author(s):  
Francis K. Buadi ◽  
Brian McClune ◽  
Yoriann S. Hull ◽  
Furhan Yunus ◽  
Sohail Minhas ◽  
...  

Abstract The addition of Rituximab to standard combination chemotherapy has significantly improved outcomes in both young and elderly patients with Non-hodgkins lymphoma (NHL). High dose chemotherapy with autologous stem cell transplant is currently the standard of care for patients with relapsed hodgkins lymphoma (HL) and NHL. However the effect of the addition of Rituximab to standard high dose chemotherapy regimen for autologous stem cell transplant on neutrophil and platelet engraftment is unknown. There are however, reported cases of neutropenia developing in patients treated with Rituximab. We performed a retrospect review of all patients with HL and NHL treated in our institution with RBEAM (Rituximab, Carmustine, Etoposide, Cytarabine, Melphalan) chemotherapy between July 2000 and June 2005 and compared it to patients receiving BEAM in the same time period. Rituximab was given at a dose of 375mg/m2 one day prior to beginning standard BEAM high dose chemotherapy. Peripheral blood was the main source of stem cells. The purpose of this study was to determine the effect of the addition of Rituximab on neutrophil and platelet engraftment. A total of 46 patients were treated during this time period. Twelve patients received RBEAM and 34 received BEAM. There was a statistical significant difference in age between the two groups. There was however no difference between the two groups in terms of race, sex and primary diagnosis. Median stem cell dose was not significantly different between the two groups. Characteristic of both groups are shown in Table: 1 Characteristics of Both Groups Median Age (yrs) Race Diagnosis Median Stem Cell Dose(x10^6) AA White HL NHL RBEAM 50.5 3 9 3 9 3.9 BEAM 36 13 21 17 17 3.8 P-VALUE 0.01 0.49 0.2 0.54 Neutrophil engraftment was defined as the first day of ANC > 500 on 3 consecutive days. Platelet engraftment was defined as the first day of platelet count > 20,000 with no platelet transfusion in the next seven days. The median time to neutrophil engraftment was 12 day in RBEAM compared to 11 days in BEAM (p=0.09). Platelet engraftment was however significantly delayed in patients receiving RBEAM 18days versus 12 days for BEAM (p= 0.02). Looking at both cohorts together we found that patients with HL had a significant delay in platelet engraftment compared to those with NHL (p=0.04). However there was no difference in neutrophil recovery. Although, stem cell dose affected neutrophil recovery, it had no effect on platelet engraftment. There was no increased toxicity in the early post transplant period associated with the addition of Rituximab. No bleeding complications resulted form the delay in platelet engraftment in the patients who received RBEAM. In a linear regression model the only factor that significantly affected engraftment was conditioning regimen. We conclude that the addition of Rituximab to standard high dose BEAM chemotherapy for autologous stem cell transplant has no effect on neutrophil engraftment; however platelet engraftment may be delayed. The continue use of this regimen despite the small delay in platelet engraftment will depend on whether there is any benefit, in terms of response rate, progression free and overall survival.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3662-3662
Author(s):  
Khaled M. Ramadan ◽  
Joseph M. Connors ◽  
Abdulwahab J. Al-Tourah ◽  
Randy D. Gascoyne ◽  
Kevin Song ◽  
...  

Abstract The effect of prior exposure to rituximab (ritux) on relapse (REL) and survival following stem cell transplantation (SCT) in patients (pts) with REL composite low and intermediate grade non-Hodgkin lymphoma (L/I-NHL) is unknown. Fifty-four pts with REL L/I-NHL underwent high-dose chemotherapy (CT) and SCT Jan ’89 to June ’05. Follow-up is complete to April ’6 with a median of 32 mo. Ritux was added to CT regimens since 2001 and given at 375 mg/m2. Eighteen pts received ritux at initial diagnosis of NHL or after REL with salvage CT prior to SCT. Pts proceeded to high dose CT with allogeneic (allo) (n=12) or autologous (auto) SCT (n=6). This group was compared with a group of pts not receiving ritux pre-SCT (n=36)(Table 1). Eleven pts (61%) are alive in the ritux group compared with 11 pts (31%) in the non-ritux group. The 2 and 4-y OS for pts who received ritux were 52% and 52%, vs 36% and 24% (p=.12, RR=.52) for pts who did not receive ritux. The EFS were significantly different with 2 and 4-y EFS for the ritux group 56% and 56% vs 24% and 18% (P=.038, RR=.42) for the non-ritux group (figure 1). No effect was seen on TRM. The risk of REL post SCT was significantly lower in the ritux group (p=.017)(figure 2). Two of 18 pts (11%) had NHL REL in the ritux vs 18 of 36 (50%) in the non-ritux group. The hazard rate of REL in pts who received ritux was 20% that of pts in the non-ritux group. Significance maintained in multivariate analysis (p=.016). No impact was seen on graft-versus-host disease (GVHD). Fifty percent and 61% of pts developed acute GVHD grades 2–4 and 50% and 64% of pts developed chronic GVHD in the ritux and non-ritux groups respectively. In conclusion, prior treatment with ritux in pts with relapsed composite L/I-NHL undergoing SCT was associated with reduced risk of REL and improved survival without associated increase in toxicity. Further analysis is underway to clarify the nature of this important finding. Table 1: Clinicopathological characteristics of ritux and non-ritux groups Parameter$ Rituximab group, n=18 (%) Non-rituximab group, n=36 (%) $ all p values are >0.1. *at diagnosis Median age at SCT 48 y 44 y M:F 2.6:1 1.6:1 Allo-SCT 12(67) 28(78) BM involvement* 10(56) 22(61) B symptoms* 7(39) 10(28) Prior purine analogue therapy 8(44) 11(31) Residual disease prior to SCT 9(50) 14(39) TBI in conditioning 13(72) 30(83) Figure Figure Figure Figure


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2872-2872
Author(s):  
Madhusmita Behera ◽  
Ambuj Kumar ◽  
Mohamed A. Kharfan-Dabaja ◽  
Benjamin Djulbegovic

Abstract Background: Primary systemic amyloidosis (AL) is a rare plasma cell clonal disorder(8/million) characterized by extracellular deposits of material composed mainly of fragments of light chain immunoglobulin throughout a body. Standard chemotherapy (e.g. melphalan and prednisone) is associated with poor outcomes (typical median survival is between 12–18 months with less than 5% survive 10 years). Autologous stem cell transplant (ASCT) has been increasingly advocated for treatment of AL. However, it is uncertain whether ASCT is better than standard chemotherapy. To address this uncertainty, we undertook a systematic review/meta-analysis to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with AL. Methods: Data search of published studies included Medline [all randomized controlled trials (RCTs)], Cochrane library and hand search of references. Studies were included if they were comparison trials of HSCT versus conventional chemotherapy, regardless if they were RCTs, prospective studies with historical control, or single arm studies. The studies were eligible if patients had biopsy proven AL with at least one major organ involved. Data were extracted on benefits as well as harms (overall survival, event-free survival, response, treatment related mortality, treatment-related morbidity). Results: Out of 34 identified studies only 13 met the inclusion criteria for the current systematic review (2 RCTs, 2 prospective non-randomized trials involving historical control, and 9 single arm trials). Altogether these trials enrolled 1056 patients. Pooled data from 4 trials with controls (RCT and non-RCT) found similar overall survival for ASCT and conventional therapy arms [hazard ratio (HR) of 1.10 (95% CI 0.88, 1.36, p=0.4); p= 0.6]. Analysis of data according to trial design also did not find any difference in survival [HR for RCTs was 1.10 (95% CI 0.88, 1.37) and for non RCTs HR was 0.98 (95% CI 0.29, 3.35)]. The complete hematological response was also similar in both arms in RCTs (Odds ratio [OR]=1.38, 95%CI 0.67, 2.85; p=0.4) and non RCTs (OR=1.78, 95%CI 0.22, 14.65; p=0.32). The pooled proportion of treatment-related deaths in the single arm studies for AHCT was 0.119 (95% CI = 0.09 to 0.14)]. Conclusion: The results from the meta-analysis indicate that there is no statistically significant difference between the treatment effects from high-dose chemotherapy with ASCT and conventional chemotherapy. Hence, the efficacy of ASCT in improving overall survival and complete hematological response remains to be proven.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5118-5118
Author(s):  
Tareq Braik ◽  
Dayra Avila ◽  
Shivi Jain ◽  
Manila Gaddh ◽  
Barabara Yim ◽  
...  

Abstract Abstract 5118 Introduction: Since the mid 1990s, high dose chemotherapy with hematopoietic stem cell rescue has been considered the standard of care for front-line treatment in younger patients with multiple myeloma. This standard of care has been based on randomized controlled trials that compared autologus stem cell transplant (ASCT) with conventional chemotherapy. During the past decade, novel agents (NA), thalidomide, bortezomib and lenalinomide, have replaced conventional chemotherapy in the treatment of myeloma. These agents, used frontline, have shown promise in improving the outcome of myeloma patients without increasing toxicity. There are no studies to date comparing NA therapy to ASCT to determine whether there is a survival difference or whether NA therapy may reduce the need for transplantation. Many of our patients have no health insurance coverage and transplant is not a therapeutic option for them. We have attempted to compare the outcome of such patients receiving NA therapy with those in the literature who received conventional chemotherapy followed by ASCT. Methods: Ninety nine patients with multiple myeloma were treated at John H Stroger Hospital of Cook County between 2001 and 2011. All patients received novel agents (thalidomide, bortezomib and lenalinomide) as part of their therapy. Only 18/99 (18.2%) went for high-dose chemotherapy with ASCT and the remaining 81/99 (81.8%) received novel therapy without ASCT. We compared the outcome of patients who received novel therapy alone to a historical control group from the literature who received ASCT with conventional therapy (N Engl J Med 2003;348:1875–83). Overall survival was determined by Kaplan-Meier estimates. Results: We evaluated 99 consecutive myeloma patients (38% males and 61% female) of which 65% were African Americans, 19% Hispanics and 7% whites. All 3 stages (international staging system) of myeloma were equally represented. The median age at diagnosis was 60 years (40–85yr). Median follow up was 48 months (12–120). During the ten year follow up period, 60 patients (60.4%) have died. Twenty four out of 99 patients (24.2%) received only one line of therapy. 75 patients received more than one line of therapy. 75% received thalidomide-based therapy, 13% received bortezomib-based therapy and 12% received lenalinomide-based therapy. The median survival of patients who received novel therapy without ASCT (n=81) was 60 months, which is higher than the median survival of the historical controls who received ASCT reported by Child et al, N Engl J Med 2003;348:1875–83, (median survival = 54.1 months), the difference was statistically significant (P=0.0329). There was no statistically significant difference between the two groups by sex (p=0.927) and race (p=0.421). The 5-year survival of patients who received novel therapy without ASCT (n=81) was 48.2%. For those who were younger than 65 years (n=54), the median survival was 72 months and the 5-year survival was 58.1% in comparison to those who were 65 years and older (n=27), the median survival was 46 months and the 5-year survival was 29.2% (P=0.029). Conclusion: Novel agents are effective frontline therapy for multiple myeloma, especially in patients younger than 65. Our cohort had remarkable results in comparison to a historical population of patients who had ASCT with conventional chemotherapy. Since there is no curative therapy to date, a prospective randomized trial comparing NA with ASCT will be essential to clarify the role of ASCT in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.


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