Flamsa Reduced-Intensity Conditioning Regimen in AML Patients – Role of Re-Induction and Disease State Prior to Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3904-3904
Author(s):  
Udo Holtick ◽  
Alexander Shimabukuro-Vornhagen ◽  
Geothy Chakupurakal ◽  
Sebastian Theurich ◽  
Silke Leitzke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Conditioning Regimen ◽  
Induction Treatment ◽  
Refractory Disease ◽  
Relapse Free Survival ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Reduced Intensity

Abstract Reduced intensity conditioning (RIC) regimens as compared to myeloablative protocols have demonstrated lower toxicity profiles at similar efficacy in the context of allogeneic haematopoietic stem cell transplantation (allo-SCT) for patients with acute myelogenous leukaemia (AML) in first or second remission. In addition, the FLAMSA RIC regimen, combining a cytoreductive part and a transplant-conditioning part, has been described to be efficacious in patients with refractory disease. Re-induction treatment after AML relapse or refractory disease is often accompanied by severe, in particular, infectious complications such as fungal pneumonia caused by long neutropenic phases, precluding a significant proportion of patients from completing allo-SCT. To have a closer look on the role of re-induction therapy prior to transplant, we retrospectively analysed clinical data of 118 consecutive patients with AML after allogeneic stem cell tranplantation following FLAMSA conditioning at our center. No prophylactic donor lymphocyte infusions were administered. Median age of the cohort was 53 years (19-73 years). Donors were matched related, matched unrelated or mismatched unrelatred in 33, 49 and 18% of the transplants. Complete remission prior to transplant was detected in 29% and 21% of the patients after induction or re-induction, respectively. Twenty-five percent of the patients were transplanted with blast persistence, both in the group of patients after first induction and re-induction treatment. Median follow-up was 27 months. The 4-yr overall survival of the whole cohort is 44% with a 4-yr relapse-free survival of 42%. Cumulative incidence of relapse was 26, 30 and 40% at one, two and four years, respectively. Cumulative incidence of non-relapse mortality (NRM) was 15, 18 and 18% at one, two and four years, respectively. There were no significant differences regarding overall and relapse-free survival for patients transplanted in CR1, CR2 or blast persistence after induction treatment. Patients who failed remission after re-induction therapy showed significantly worse overall and relapse-free survival (p=0,049 and 0,003, repectively, log-rank test). NRM was similar in all cohorts. FLAMSA is a highly effective conditioning regimen for AML patients even not in CR. Thus, the decision for re-induction therapy prior to allogeneic SCT has to be weighted against the potential toxicity of this approach. Disclosures No relevant conflicts of interest to declare.

High-dose chemotherapy followed by allogeneic stem cell transplantation in high-risk relapsed and refractory aggressive non-Hodgkin lymphoma: Results of a prospective study of the German high-grade non-Hodgkin lymphoma study group.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Gerald Wulf ◽  
Peter Dreger ◽  
Michael Pfreundschuh ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Refractory Disease ◽  
Reduced Intensity Conditioning ◽  
Early Relapse ◽  
Non Hodgkin Lymphoma ◽  
Reduced Intensity

8004 Background: The role of allogeneic stem cell transplantation (alloSCT) in high-risk aggressive NHL is poorly defined; the role of graft-versus-lymphoma effect is unclear. Reduced intensity conditioning has shown limited efficacy in patients with refractory disease. Methods: Patients with primary refractory disease, early relapse (<12 months) or relapse after autologous SCT of aggressive B-cell (n=61) or T-cell (n=23) NHL were enrolled from June 2004 to March 2009. Myeloablative conditioning (fludarabine 125mg/m2, busulfan 12mg/kg, cyclophosphamide 120 mg/kg) was followed by alloSCT from related (n=24) or unrelated (n=60) donors. 57/84 patients received a 10 HLA-loci compatible graft. Results: Overall survival at 3 years was 42% (95% CI, 31% to 52%), progression-free survival (PFS) was 40% (95% CI 29% to 50%). Non-relapse mortality (NRM) was 12% at 100 days and 35% at one year. Graft-versus-host disease (GVHD) and infection were the predominant causes of NRM. Relapse rate was 30% with latest relapse at day +327. Patients with an HLA fully compatible donor (plus ATG with unrelated donors) (n=40) had the best outcome (NRM at 1y 10.4 vs 57.2%, PFS at 3y 64.7% vs 31.8%, p < 0.0001). GVHD > grade I correlated with improved PFS (HR 0.45, p=0.0088). Patients with refractory disease or early relapse (n=60) experienced PFS at 3y of 33%. Conclusions: Lymphoma-debulking (high-dose) chemotherapy followed by alloSCT shows excellent results in heavily pretreated patients with early relapse or primary refractory aggressive lymphoma. There was evidence of graft-versus-lymphoma activity in this setting. For patients with a fully matched (10/10) related or unrelated donor the results compare favorably to autoSCT or alloSCT following reduced-intensity conditioning.

Low Progression-Free Survival for High-Risk Patients Treated with Reduced-Intensity Conditioning Regimen Allogeneic Stem Cell Transplantations with Volunteer Unrelated Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5432-5432
Author(s):  
Reza Tabrizi ◽  
Fontanet Bijou ◽  
Krimo Bouabdallah ◽  
Thibaut Leguay ◽  
Gerald Marit ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Acute Gvhd ◽  
Progression Free Survival ◽  
Refractory Disease ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Risk Patients ◽  
Reduced Intensity

Abstract Reduced-intensity conditioning regimens (RICR) are increasingly used before allogeneic stem cell transplantation (SCT) for patients not eligible for myeloablative conditioning. The relapse and survival rates after RICR allogeneic SCT were studied in 19 high-risk patients treated between February 2002 and December 2004. Ten males and 9 females with a median age of 47 years (15–55) received PBSC transplantation from a 10/10 (n=15) or 9/10 HLA antigen-matched donor (n=4). Acute leukemia was the main diagnoses (n=12; 6 AML and 6 ALL), the other diagnoses were 3 multiple myeloma, 2 CML, 1 NHL, 1 CLL. All patients had high-risk disease: 12 had second or &gt; 2 complete remission, 5 second partial remission and 2 refractory disease. The preparative regimen consisted of cumulative dose of Busulfan 8mg/kg, Fludarabine 150 mg/m2 and ATG 7.5 mg/kg (Thymoglobulin, Genzyme, Lyon, France). Graft-versus-host disease (GVHD) prophylaxis regimen consisted of cyclosporine A and short-course methotrexate. Median follow-up was 14 months (5–39 months). Engraftment was complete in all but 2 patients with refractory disease and 14 patients achieved 100% donor CD3 (median 56 days, range 18–123). Grade 2 to 3 acute GVHD was seen in 3 (16%) patients, no grade 4 acute GVHD was observed. Grade 1 chronic GVHD was seen in 1 patient. Nine pts relapsed at a median time of 9.5 months, 3 pts had never reached a full CD3 donor chimerism. Twelve pts are alive, seven pts in complete remission, 2 pts with relapsed disease. Three pts relapsed and achieved a subsequent complete remission by chemotherapy, one of them received a second SCT, one a DLI and one other developed hepatic cGVHD and didn’t receive DLI. Five pts died from recurrent disease, One pt died from cerebral toxoplasmosis and one other from cerebral hemorrhage due to a secondary poor graft function. Survival rate was 73% (95% CI 0.52–0.93) at 6 months and 60% (95% CI 0.38–0.83) at 1 year. PFS rate was 73% (95% CI 0.52–0.93) at 6 months and 33% (95% CI 0.09–0.57) at 1 year. In conclusion, in this cohort of pts, the progression-free survival is unsatisfactory. This can be explained by the advanced stage diseases and the low incidence of cGVHD, probably due to high immunosuppressive treatment. A less intensive immunosuppressive protocol can be tested to improve the results in this particular group of patients. Figure Figure Figure Figure

Allogeneic Stem Cell Transplantation With Reduced Intensity Conditioning Regimen In Patients With Relapsed Hodgkin´s Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5511-5511
Author(s):  
Maria Marta Rivas ◽  
Mariano Berro ◽  
Sebastian Yantorno ◽  
Maria Virginia Prates ◽  
Jorge H Milone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract Introduction Hodgkin´s Lymphoma (HL) is a highly curable disease. However, there are still patients with primary refractory disease or who relapse after first-line treatment, or even after high-dose chemotherapy with hematopoietic cell rescue. Allogeneic stem cell transplant (ASCT) is therapeutic for this patients. Objective To analyze the experience with relapsed HL patients that received ASCT with reduced intensity conditioning (RIC)regimen in 8 Argentine Medical Centers. Design and Population We performed a retrospective multicenter analysis from data obtained from medical records. Fifty-four patients with relapsed HL who received ASCT had a median age of 26years. The relationship between male / female was 1/1. Only 3 patients (5.5%) at the time of transplant had a performance status> 1 according to ECOG. Ninety-six percent of the patients had received previously autologous transplant. Most patients 43 (80%) received an identical sibling donor transplant. All patients receiving unrelated donor transplants had in vivo lymphocyte depletion as prophylaxis of graft versus host disease. Forty-three patients (79.6%) received as a conditioning regimen Fludarabine + Melphalan. The disease status at transplant was: complete remission (CR) 33%, partial remission (PR) 54%, stable disease / progressed (SD / PD) 13%. Results With a median follow up of 2.7 years, actuarial overall survival (OS) at 1 and 5 years was 65% and 20% respectively and disease free survival (DFS) at 1 and 5 years was 35 % and 18% respectively. The incidence of acute GVHD grade II-IV was 31%. Patients in CR at the time of transplant showed significant differences compared with those who were not in CR in DFS (1-5 years 52-27% vs 19-14%, p=0.01), OS (1-5 years 76-38% vs 59-13%, p=0.02) and non relapsed mortality (NRM) (1-5 years 6-12% vs 34-39%, p=0.04). Age, PS, the use Fludarabine + Melphalan as conditioning regimen, unrelated donor, aGVHD, were not variables that modified the overall survival and disease-free survival. Conclusion The ASCT with RIC regimen is a feasible therapeutic option in patients with HL, especially in patients who can achieve CR. The low rate of DFS is still an issue in this setting, may be new drugs may help in optimizing pretransplant response status to improve patients’ outcome. Disclosures: No relevant conflicts of interest to declare.

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