scholarly journals Efficacy of Maintenance Therapy after Autologous Hematopoietic Stem Cell Transplantation in High-Risk Aggressive Lymphoma: A Single-Center Prospective Non-Randomized Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5753-5753
Author(s):  
Yongquan Chen ◽  
Zhihong Zheng ◽  
Xiaofeng Luo ◽  
Jinhua Ren ◽  
Haili Geng ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Disease Free Survival ◽  
Aggressive Lymphoma ◽  
Observation Group ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free ◽  
Maintenance Group

Abstract OBJECTIVE: Relapse after autologous hematopoietic stem cell transplantation (ASCT) is still challenging for high-risk aggressive lymphoma. This study was to investigate the efficacy and safety of maintenance therapy post-ASCT. METHODS: From June 2009 to March 2018, patients with high-risk aggressive lymphoma in our hospital were treated with maintenance therapy post-ASCT according to the patient's wishes, and then assigned to maintenance group or observation group. The end point of follow-up was disease progression or death. The 3-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups. RESULTS: A total of 79 patients were enrolled, with a median age of 38 years (8-64 years), 50 males and 29 females. IPI score ≥2 points in 28 cases, stage III-IV in 58 cases, B symptoms in 21 cases, Extranodal lesions ≥ 2 in 17 cases, bone marrow infiltration in 15 cases, and 24 cases with partial remission (PR) prior to ASCT. In addition to 2 cases of early death, the remaining 77 patients with lymphoma were underwent successfully transplantation and achieved CR post-ASCT. 54 patients were assigned to the observation group, and 23 patients to the maintenance group, including 17 with rituximab and 6 with DPP/DCEP-G alternation regimen. There were no s ignificant differences in gender, age, pre-transplant disease status, and hematopoietic reconstitution between the two groups. The main causes of death were disease recurrence. No serious adverse reactions occurred during the maintenance treatment period. After a median follow-up of 616 days (12-2854 days), the relapse rates of the observation group and the maintenance group were 49.1% vs 12.9%, and the DFS of the 1st, 2nd, and 3rd years were 62.8% VS 93.8%, 48.1% VS 87.1%, and 45.3% VS 87.1% (P = 0.007), respectively. The OS of the 1st, 2nd, and 3rd years were 89.3% VS 100%, 83.2% VS 92.9%, and 76.2% VS 92.9% (P=0.212), respectively. Conclusion: Maintenance therapy post-ASCT could reduce the risk of relapse and promote disease-free survival, which deserves further investigation. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem-Cell Transplantation Using a Reduced-Intensity Conditioning Regimen Has the Capacity to Produce Durable Remissions and Long-Term Disease-Free Survival in Patients With High-Risk Acute Myeloid Leukemia and Myelodysplasia

2005 ◽  
Vol 23 (36) ◽  
pp. 9387-9393 ◽  
Author(s):  
Sudhir Tauro ◽  
Charles Craddock ◽  
Karl Peggs ◽  
Gulnaz Begum ◽  
Premini Mahendra ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Purpose The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. Patients and Methods Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). Results The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. Conclusion The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.

Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning (RIC) Regimen Has the Capacity To Produce Durable Remissions and Long Term Disease-Free Survival in Patients with High Risk Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1141-1141
Author(s):  
S. Tauro ◽  
S. Mackinnon ◽  
K. Peggs ◽  
G. Begum ◽  
P. Mahendra ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract The toxicity of allogeneic stem cell transplantation (SCT) can be substantially reduced by the use of a reduced intensity conditioning (RIC) regimen and this has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with AML and MDS has not yet been defined and consequently their role in the management of these diseases remains conjectural. Seventy-six patients with high risk AML or MDS were allografted using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range 18–71 years). There were 46 males and 30 females; 41 patients received an allograft from an unrelated donor and 35 from a matched sibling donor. The 100 day transplant related mortality was 9% and no patient developed greater than Grade 2 graft-versus-host disease (GVHD). With a median follow-up of 36 months (range 13–70 months) 27 patients were alive and in remission with a 3y actuarial overall survival (OS) and disease-free survival (DFS) rate of 41% and 37% respectively. The 3y OS and DFS of patients with AML in complete remission (CR) at the time of transplantation was 48% and 42% respectively. In a multivariate setting, Cox regression analysis demonstrated prognostic significance of disease stage at the time of transplant with improved DFS in patients with AML in CR at the time of transplantation (HR=2.03, 95% CI=1.02–4.07). Disease relapse was the commonest cause of treatment failure occurring at a median time of 6 months post-transplant. Fourteen out of 27 (52%) patients relapsed within 6 months and 23/27 (85%) within twelve months defining a relatively narrow window for therapeutic intervention to prevent disease recurrence. The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts are capable of producing sustained disease free survival in a significant number of patients with AML who would be ineligible for allogeneic transplantation using a myeloablative conditioning regimen.

Impact of Molecular Markers and Cytogenetic Abnormalities on Long-Term Overall Survival and Disease-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Acute Myeloid Leukemia (AML) patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4476-4476
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Xavier Thomas ◽  
Carole Charlot ◽  
Fiorenza Barraco ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Allogeneic Hsct ◽  
Disease Free

Abstract We performed a retrospective analysis from our transplant registry on first allogeneic hematopoietic stem cell transplantations (HSCT) for acute myeloid leukemia (AML) patients (pts) between 1996 and 2007. Our principal objective was to analyze the impact of molecular markers on the long-term overall and disease-free survival (OS and DFS) after first allogeneic HSCT. We found 364 pts, only 63 pts had retrospectively available conserved cells at diagnosis. The expression levels of WT1, Evi1, Flt3 and Hoxa9 were performed by quantitative RT-RQPCR. The mutational status of MLL duplication, FLT3 (internal tandem duplication or nucleotide substitutions) (ITD), NPM1 and CEBPα were determined by PCR, RFLP and/or sequencing analysis. All pts except 1 had a karyotype analysis at diagnosis. Among these 63 pts, there were 27 (43%) males and 36 (57%) females, with a median age of 41 years (18-64). The FAB classification was M0: 6, M1: 10, M2: 13, M4: 6, M5: 21, M6: 3, M7: 1 and 3 unclassified. Concerning the karyotype analysis, 25 (40%) pts had a normal karyotype, 37 (60%) pts presented cytogenetic abnormalities classified as favourable prognosis in 5 cases (8%), intermediate in 13 cases (21%) and poor in 19 cases (31%). Regarding the molecular markers evaluated in all pts: 4(6%) pts had Flt3over-expressed (ov-ex), 19 (30%) FLT3 ITD+, 3 (5%) MLLdup, 10 (16%) Hoxa9 ov-ex, 7 (11%) Evi1 ov-ex, 15 (24%) NPM1mut+, 25 (40%) WT1 ov-ex and 1 CEBPαmut+ (this marker was evaluated only in 12 pts). Associations between these markers and the karyotype prognosis groups are shown in Figure1. Twenty three (36%) pts had no abnormal molecular markers and 40 (54%) pts had at least one abnormal marker: 10 (16%) 1 marker, 10 (16%) 2 markers, 12 (19%) 3 markers, 4 (6%) 4 markers and 4 (6%) 5 markers. Concerning the karyotype, among the 23 negative molecular pts, 22 have been evaluated and there were 9 (41%) normal, 11 (50%) poor and 2 (9%) favourable; and among the 40 positive pts, 16 (40%) were normal, 8 (20%) poor, 13 (32.5%) intermediate and 3 (7.5%) favourable. Concerning transplantation, 50% of HSCT were done after 2004 and the median interval between diagnosis and transplantation was 6 months (2.6–68.5). Before conditioning, 41 pts were in CR (26 CR1, 14 CR2 and 1 CR3), 8 in PR and 14 in relapse. Twenty five (40%) pts received a non-myelo-ablative conditioning and 38 (60%) a myelo-ablative one. There were 34 sex-mismatched (21 M→F and 13 F→M), 21 ABO incompatibility (6 minor and 15 major), 55 were HLA matched and 8 mismatched. Twenty three (36.5%) pts received PBSC, 37 (59%) bone marrow and 4 (6.5%) cord blood cells from 47 (75%) HLA siblings and 16 (25%) unrelated donors. After transplantation, 59 (94%) pts engrafted, 42 developed AGVHD (21gr1, 13 gr2 and 8 gr4), and among 51 evaluable pts, 13 developed cGVHD (7 limited and 6 extensive). At the last follow-up, 20 pts have relapsed, 29 pts are alive (28 CR and 1PR) and 34 died [18 (53%) from TRM and 16 (47%) from relapse]. At the median follow-up of 48 months, the OS and DFS for the whole population were 40% (33–47) and 40% (34–46) respectively with a maximum follow-up of 130 months and for the different subgroups according to karyotype and molecular markers the results are shown in Table 1. The univariate analysis showed a significant impact of FLT3 ITD and over-expression of FLT3RQ on long-term DFS, (p=0.03 and p=0.02 respectively), and a trend on long-term OS (p=0.08). Concerning the karyotype and some other markers (MLL, EVI1, NPM1 and Hoxa9), we did not observe any significant difference because of small number of pts in some subgroups. The known benefic impact of NPM1mut+, was erased because the majority of this group presented an associated FLT3 ITD+. In addition, we are performing a multivariate analysis that will be presented. In conclusion, allogeneic HSCT in this high risk population of AML pts, allowed a good probability of long-term OS and DFS, despite the presence of high number of bad molecular markers and cytogenetic abnormalities. Finally, AML pts with FLT3 ITD+ seem not benefit from allogeneic HSCT as well as patients with NPM1mut+ associated with FLT3ITD+. Figure 1. Frequencies and distribution of different molecular markers and karyotype subgroups Figure 1. Frequencies and distribution of different molecular markers and karyotype subgroups Table 1. OS and DFS according to different molecular markers and karyotype subgroups

Disease-Free Survival Of Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation Is Not Associated With Disease Status and Donor Sources

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2158-2158
Author(s):  
Yue Lu ◽  
Tong Wu ◽  
Xing-Yu Cao ◽  
Yan-Li Zhao ◽  
De-Yan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Disease Status ◽  
Refractory Anemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is an only curative modality currently for myelodysplastic syndrome (MDS). High-risk MDS usually has lower complete remission (CR) rate and higher chemotherapy-related mortality compared with de novo acute myeloid leukemia (AML). To examine whether CR before HSCT has survival benefit for MDS treated by HSCT, we retrospectively analyzed the data during 11 years from our center. The clinical outcomes of MDS after HSCT from different donor sources have also been evaluated. Objective In present clinical study, the effects of disease status and donor sources on disease-free survival (DFS) of MDS after HSCT were studied. Methods From August 2001 to December 2012, total 122 patients with MDS that underwent HSCT in our center were enrolled. Male to Female was 76: 46. The median age was 35 (8 to 57) years old. The median blasts in bone marrow (BM) before conditioning were 9% (1% to 65%). According to 2008 WHO classification, the patients were diagnosed as refractory cytopenias with unilineage dysplasia (RCUD) in 12, refractory anemia with ring sideroblasts (RARS) in 2, 5q- in 1, refractory cytopenias with multilineage dysplasia (RCMD) in 15, refractory anemia with excess blasts (RAEB) -1/RAEB-2 in 36 and transformed AML in 56. For International Prognostic Scoring System (IPSS), 12 patients were in low-risk, 27 in intermediate-1, 24 in intermediate-2, and 59 in high-risk. Based on BM blast percentage pre-conditioning, 47 cases were less than 5%, 43 patients were between 5% to 20%, and 32 cases were more than 20%. The stem cells were from identical siblings (45) or unrelated donor (24) or haploidentical family members (53). Conditioning regimens were BUCY/BUFLU for identical sibling HSCT, and BUCY/BUFLU plus ATG (Thymoglobuline, 8-10mg/kg) for unrelated or haploidentical transplants. Graft-versus-host disease prophylaxis was employed by Cyclosporin A, Methotrexate and Mycophenolate mofetil as reported previously (DP Lu et al., Blood 2006; 107:3065). Results: With median follow-up 31 (1-144) months, DFS was 73.8%. Fourteen patients (11.4%) relapsed. Transplant-related mortality was 14.8%. No significant differences on DFS were found among RCUD/RARS/5q- (68.8%), RCMD (85.7%), RAEB-1/RAEB-2 (72.2%) and transformed AML (73.2%) (p=0.761). A similar DFS was seen in different risk categories (73.3% in low-risk, 79.2% in intermediate-1, 75.0% in intermediate-2 and 71.2% in high-risk; p=0.861). Moreover, CR or not before HSCT has no remarkable effect on DFS (blasts <5%, 78.7%; blasts 5% to 20%, 67.4%; blasts > 20%, 75.0%; p=0.342). Donor sources have also no significant effects on DFS (identical sibling 75.6%, unrelated donor 79.2%, haploidentical family member 69.8%; p=0.651). Conclusions Our clinical results have shown that under current protocol, DFS of MDS after allogeneic HSCT is quite encouraging no matter the disease status and stem cell donor sources. Therefore, it is not necessary that complete remission is achieved by chemotherapy before transplant. Haploidentical family member is an important alternative donor for patients with MDS when matched either identical sibling or unrelated donor is not available. Disclosures: No relevant conflicts of interest to declare.

Induction Therapy with Dasatinib and Prednisone for Patients with Philadelphia Positive ALL

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4907-4907
Author(s):  
Abhishek Chilkulwar ◽  
Salman Fazal ◽  
Jocelyn T. De Yao ◽  
Parik Padhi ◽  
Cyrus Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Therapy ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Comorbidity Index ◽  
High Comorbidity ◽  
Disease Free ◽  
Matched Donor

Abstract Background: The addition of a Tyrosine Kinase Inhibitor (TKI) to induction chemotherapy has improved the outcome of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). However, the treatment related mortality and morbidity of intensive treatment increases with age. The use of a TKI alone for induction is less toxic and yields CR rates comparable to combined therapy. Eligibility for post remission hematopoietic stem cell transplantation is less likely to be compromised with TKI induction. We present a retrospective review of patients with Ph+ ALL treated at our institution with dasatinib and prednisone induction who subsequently underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) as post remission therapy. Methods: We retrospectively identified 15 patients with Ph+ ALL treated at our institution between February 2012 and June 2015. Patients received induction therapy with dasatinib at 100 mg or 140mg daily till complete hematological response. Prednisone 60 mg/m2/day (capped at 120 mg daily) was administered until day 24 and then tapered and stopped at day 32. Intrathecal chemotherapy with MTX and Ara-C were administered twice during the induction period. Dasatinib dose reduction/discontinuation was permitted for non-hematological toxicity. Patients who achieved remission proceeded to allo-HSCT if a suitable HLA-matched donor was available. Patients who did not have a suitable HLA matched donor received TKI + POMP maintenance. We calculated CHR, CCyR, disease-free survival (DFS) and overall survival (OS). Results: The median age of patients treated with dasatinib plus prednisone was 62 years (range: 19-73). Baseline patient and disease characteristics are summarized in Table 1. Median WBC count was 22.5 x 109/L. Fourteen of 15 patients treated with dasatinib achieved a CHR (93.3%), 1 patient did not undergo a bone marrow biopsy but had normal blood counts. Median time to CHR was 42 days (range: 22-69). CCYR was obtained in 11 patients (73%) and MMR was achieved in 5 patients (33%). No patient died during induction therapy. The 14 patients who were in CHR after induction, underwent allo-HSCT (n=7), are being evaluated for allo-HSCT (n=3), were unable to undergo allo-HSCT due to a high comorbidity index and/or lack of a suitable donor (n=3) or were lost to follow-up (n=1). Of the 3 patients who were unable to undergo allo-HSCT, 2 patients continue on dasatinib maintenance and 1 patient takes ponatinib. Of 8 patients not yet transplanted 3 relapsed, while only 1 relapse was seen in 7 patients who underwent allo-HSCT. Median DFS was 315 days (range: 57-1061) and median OS was 354 days (range: 107-1082) corresponding Kaplan Meier curves for OS and DFS are shown below. Conclusions: In our adult Ph+ ALL patients induction therapy with dasatinib and prednisone was effective and well tolerated. Patients achieving CHR were able to undergo allo-HSCT with curative intent. This strategy retrospectively appears equal or better than results with induction chemotherapy of conventional variety. Table 1. Patient characteristics Male sex, n (%) 5 (33.3) Age <20, n (%) 1 (6.7) 20-49, n (%) 1 (6.7) ³50, n (%) 13 (86.6) Median (range) 62 (19-73) Median follow-up in months (range) 11.7 (4.1-40) Presenting WBC x 10 9/L < 30, n (%) 8 (53.3) ³ 30, n (%) 7 (46.7) Median (range) 22 (2.8-358.4) Bcr-Abl type p190, n (%) 12 (80) p210, n (%) 2 (13.3) P190 and p210, n (%) 1 (6.7) Bcr-Abl level (1 unknown)* Mean (range) 35.1 (1.8-194.4) Median time to CHR in days (1 unknown), (range) 41.5 (22-69) Induction dose of dasatinib 70mg BID, n (%) 1 (6.7) 100mg daily, n (%) 8 (53.3) 140mg daily, n (%) 6 (40) CCyR after induction achieved, n (%) 11 (73.3) MMR achieved after induction, n (%) 5 (33.3) Dasatinib Dosing after Induction None, n(%) 1 (6.7) 70mg BID, n(%) 1 (6.7) 100mg/day, n(%) 12 (80) 140mg/day, n(%) 1 (6.7) POMP + TKI post induction, n(%) 4 (26.7) Post remission therapy (3 being evaluated for transplant, 1 never achieved CHR, 1 lost to ff-up)+ Transplant, n (%) 7 (46.7) Ponatinib, n (%) 1 (6.7) Dasatinib, n (%) 1 (6.7) HyperCVAD±, n (%) 1 (6.7) TKI maintenance after transplant, n (% of transplanted) 3 (42.9) M351T mutation, n (%) 1 (6.7) F317L mutation, n (%) 1 (6.7) Bcr-Abl detection by PCR with unit in ratio (international scale), +poor performance status or high comorbidity index is the reason for no transplant, ±hyperCVAD initiated but not tolerated. Figure 1. Overall Survival. Figure 1. Overall Survival. Figure 2. Disease Free Survival Figure 2. Disease Free Survival Disclosures Fazal: Novartis: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Off Label Use: Dasatinib use for newly diagnosed Ph+ ALL.

Combined modality therapy for tumor stage mycosis fungoides: results of a 10-year follow-up.

1988 ◽  
Vol 6 (7) ◽  
pp. 1177-1183 ◽  
Author(s):  
D E Hallahan ◽  
M L Griem ◽  
S F Griem ◽  
M Medenica ◽  
K Soltani ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Mycosis Fungoides ◽  
Combined Modality Therapy ◽  
Disease Free Survival ◽  
Initial Response ◽  
Tumor Stage ◽  
Free Survival ◽  
Combined Modality ◽  
Disease Free

Twenty-one patients with tumor stage mycosis fungoides (MF) with or without lymph node (LN) involvement, were treated with total skin electron beam irradiation (TSEB) followed by six monthly cycles of systemic chemotherapy (CT) of either mechlorethamine (HN2) or cyclophosphamide (CTX) with vincristine (VCR), procarbazine, and prednisone (PRD) (COPP or MOPP). All patients had complete clearing of the skin after TSEB. However, while receiving chemotherapy, two patients developed visceral involvement and eight patients relapsed with limited cutaneous plaques (LCP). The median duration of remission was 12 months from the completion of TSEB, and all patients relapsed with cutaneous plaques within 25 months. Complete remission was again achieved using additional electron irradiation and maintenance therapy in all but one patient. Multiple cutaneous recurrences occurred in all patients. Median survival from the initiation of TSEB is 6 years. Five patients are living beyond 8 years (four off treatment without disease for 1 to 7 years). LN involvement did not influence initial response or survival. Combined modality therapy for tumor stage MF using TSEB followed by systemic CT and subsequent maintenance therapy may lead eventually to prolonged disease-free survival (DFS) in selected patients.

scholarly journals Disease-free survival after autologous bone marrow transplantation in patients with acute myelogenous leukemia

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 1898-1904 ◽  
Author(s):  
M Korbling ◽  
W Hunstein ◽  
TM Fliedner ◽  
S Cayeux ◽  
B Dorken ◽  
...  
Keyword(s):  
High Risk ◽  
Autologous Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Autologous Bone Marrow ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
Acute Myelogenous ◽  
Autologous Bone ◽  
Disease Free

Autologous bone marrow transplantation (ABMT) makes it possible to escalate the dose of cytotoxic treatment to a lethal range. Disease- free survival (DFS) following myeloablative therapy and ABMT has been shown to be superior to conventional treatment in high risk patients with acute myelogenous leukemia (AML). It was the purpose of the present study to compare hematopoietic reconstitution, actuarial DFS, and relapse rate of patients transplanted in first complete remission (CR) of AML with those in second or subsequent CR, and to evaluate transplant related mortality. Fifty-two patients with AML, 22 in first CR (low risk) and 30 in second or subsequent CR (high risk), underwent total body irradiation (12.1 to 16.7 Gy) and cyclophosphamide (CY) treatment (200 mg/kg) followed by ABMT. The autograft was incubated with the active CY derivative Mafosfamide (ASTA Werke, Bielefeld, Federal Republic of Germany) to reduce the number of possibly contaminating clonogenic tumor cells. All patients showed three lineage engraftments with platelet recovery observed as being the slowest. The transplant related death rate was low at 5.8%. There was no significant difference in the kinetics of polymorphonuclear (PMN) cell or platelet reconstitution between the low and high risk patient subgroups. The estimated probability of DFS (relapse) after ABMT in first CR was 61% (36%) compared with 34% (65%) in second or subsequent CR, the longest follow-up being 55 months and 57 months, respectively (median follow-up 31 months and 19 months, respectively). ABMT offers a stable long-term DFS when performed in first CR with no relapses occurring in over a year after transplantation. Six later relapses, however, were seen after ABMT in second or subsequent CR, although DFS was not statistically different from that of first remission patients (P = .72).

Adjuvant Treatment of High-risk Adult Soft Tissue Sarcomas: A Survey by the Italian Sarcoma Group

2006 ◽  
Vol 92 (2) ◽  
pp. 92-97 ◽  
Author(s):  
Sergio Frustaci ◽  
Massimiliano Berretta ◽  
Alessandro Comandone ◽  
Ettore Bidoli ◽  
Antonino De Paoli ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Soft Tissue ◽  
Survival Rates ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Overall Survival Rates

Aims and Background After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice. Methods A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 μg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles. Results From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively. Conclusions The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.

scholarly journals 3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT

2019 ◽  
Vol 23 (64) ◽  
pp. 1-88 ◽  
Author(s):  
Timothy Iveson ◽  
Kathleen A Boyd ◽  
Rachel S Kerr ◽  
Jose Robles-Zurita ◽  
Mark P Saunders ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Treatment Group ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Background Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. Objectives To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. Design An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. Setting A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. Participants Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. Interventions The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. Main outcome measures The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. Results Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand–foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4–6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. Conclusions The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019–20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. Trial registration Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre – Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894).

Sign in / Sign up

Export Citation Format

Share Document