scholarly journals Long-term follow-up of a retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic transplantation from matched related donors in myelodysplastic syndromes

2017 ◽  
Vol 52 (8) ◽  
pp. 1107-1112 ◽  
Author(s):  
R Martino ◽  
◽  
A Henseler ◽  
M van Lint ◽  
N Schaap ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Retrospective Comparison ◽  
Long Term Follow Up ◽  
Reduced Intensity

Long-term follow-up of a phase I study of high-dose decitabine, busulfan, and cyclophosphamide plus allogeneic transplantation for the treatment of patients with leukemias

Cancer ◽  
2003 ◽  
Vol 97 (5) ◽  
pp. 1242-1247 ◽  
Author(s):  
Marcos de Lima ◽  
Farhad Ravandi ◽  
Munir Shahjahan ◽  
Borje Andersson ◽  
Daniel Couriel ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Long Term Follow Up

Long Term Follow-up of the Prospective Multicenter Study of reduced-Intensity Allogeneic Stem Cell Transplantation for Primary or Post ET/PV Myelofibrosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1019-1019 ◽  
Author(s):  
Haefaa Alchalby ◽  
Tatjana Zabelina ◽  
Daniel Wolff ◽  
Guido Kobbe ◽  
Martin Bornhäuser ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Allogeneic Transplantation ◽  
Prospective Multicenter Study ◽  
Long Term Follow Up ◽  
Reduced Intensity

Abstract Abstract 1019 Allogeneic stem cell transplantation is the only curative treatment for myelofibrosis. Here we present a long–term follow up of patients with myelofibrosis treated with reduced-intensity allogeneic stem cell transplantation in the prospective multicenter study conducted by the MDS subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) (study registration NCT 00599547). From 2002 to 2007, a total of 103 patients with primary (63 pts) or post-polycythemia vera and –essential thrombocythemia myelofibrosis (40 pts) from seventeen transplantation centers in three nations were included in the study. There were 62 males and 41 females with a median age of 55 years (range, 32–68 years). Risk profile according to Lille score was low risk with constitutional symptoms (17%), intermediate risk (53%) and high risk (30%). All but three of the patients received peripheral stem cells as stem cell source from either related (n=33) or unrelated donor (n=70) and a conditioning with Busulfan (10mg/kg orally or 8mg/kg intravenously),Fludarabin (180 mg/m2) and antithymocyte-globulin (ATG-Fresenius®) according a previously published protocol. According to high-resolution HLA typing, 21 patients had at least one allele or antigen HLA mismatch. From 88 patients with a known JAK2V617F-status 63 harbored the mutation. After a median follow up of 60 months (range 9–109 months), 41 patients had chronic graft vs. host disease which was extensive in the half of cases. The 5-year and 8-year estimated overall survival (OS) was 68% and 65%, respectively with a stable plateau after 5,3 years follow up (Figure-1). Estimated 5-year disease-free survival was 40%. The cumulative incidence of relapse/progression at 3 and 5 years was 22% and 28% and the non-relapse mortality at 1 and at 3 years was 18% ands 21%, respectively.Figure-1Figure-1. Within the overall follow up period, relapse/progression occurred in 28 patients. Twenty one of them were treated with donor-lymphocyte infusions (DLI) and/or a second allogeneic transplantation (n=11). Sixteen of those were at the last follow up alive. The estimated OS of all relapsed patients after a median follow up of 46 months (range 4–62 months) beginning from the time of relapse was 55%. In multivariate analysis advanced age >55years (HR: 4.69, p=0.001), absence of JAK2V617F mutation (HR: 2.50, p=0.02), mismatched donor (HR: 3.62, p=0.002) were significant independent predictors for reduced OS. This update of a prospective trial using reduced intensity conditioning followed by allogeneic stem cell transplantation for myelofibrosis confirmed a very good long-term OS. Relapse still occurs in about 30% and remains the main problem after transplantation. However, with adoptive immunotherapy using DLI or even second allogeneic transplantation a second remission with long term survival can be induced in about 50% of the relapsed patients. Developing methods for remission monitoring and early prediction and treatment of relapse should be the focus of future studies. Disclosures: Kobbe: Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy. de Witte:Novartis: Consultancy, Honoraria, Speakers Bureau.

Allogeneic Hematopoietic Stem-Cell Transplantation In AML and MDS Using Myeloablative Versus Reduced Intensity Conditioning: 10 Years Later

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4635-4635
Author(s):  
Avichai Shimoni ◽  
Noga Shem-Tov ◽  
Yulia Volchek ◽  
Ivetta Danylesko ◽  
Ronit Yerushalmi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Reduced Intensity Conditioning ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Long Term Follow Up ◽  
Relapse Rates ◽  
Active Disease ◽  
Reduced Intensity

Allogeneic stem cell transplantation (SCT) with both myeloablative (MAC) and reduced intensity conditioning (RIC) is effective therapy in AML and MDS. However, the relative merits of each may differ in different settings. There is paucity of data on the long-term outcome (beyond 10 years) following RIC due to the relative recent introduction of this approach. We have previously reported on the role of dose intensity in a group of 112 patients (pts) with AML/MDS given SCT with different regimens between 1999 and 2004 (ASH 2004, Leukemia 2005). We showed that overall survival (OS) was similar with MAC and RIC in pts given SCT in remission, but was inferior in pts given RIC in active disease due to high post SCT relapse rates. We have now updated SCT outcomes in the same cohort with a median follow up of 10 years (range, 8.5-12.5) in order to better predict long-term outcome and confirm whether late events may have changed the initial conclusions. The median age at SCT was 50 years (18–70). Eighty-five pts had AML and 17 had MDS (IPSS int2 or high). Fifty-eight had active disease at SCT (>10% marrow blasts) and 54 were in remission. The donor was HLA-matched sibling (n=58), 1-Ag mismatched related (n=6) or matched-unrelated (n=48). Twenty-nine pts (26%) had poor risk cytogenetics. Forty-five pts met eligibility criteria for standard MAC and were given intravenous-busulfan (ivBu, 12.8 mg/kg) and cyclophosphamide (BuCy). Sixty-seven pts were considered non-eligible for standard MAC due to advanced age, extensive prior therapy, organ dysfunction or poor performance status. These pts were given RIC with fludarabine and ivBu (6.4 mg/kg, FB2, n=41) or reduced toxicity conditioning (RTC) with fludarabine and myeloablative doses of ivBu (12.8 mg/kg, FB4, n=26). The median age of RIC/RTC and MAC recipients was 55 and 42 years, respectively (p=0.001) and a larger proportion of RIC/RTC recipients had unrelated donors (p=0.01). In all, 38 pts are alive and 74 have died, 48 relapse, 26 non-relapse mortality (NRM). Overall survival (OS) at 10 years was 44% and 31% after MAC and RIC/RTC, respectively (p=0.22). Active disease at SCT and poor-risk cytogenetics were the most significant factors predicting reduced OS in multivariable analysis, HR 2.0 (p=0.05) and 2.7 (p=0.003), respectively. Advanced age, secondary disease, donor and conditioning type had no prognostic significance. MAC and RIC/RTC had similar outcomes when leukemia was in remission at SCT; 10-year OS been 47%, 50% and 47% after BuCy, FB4, and FB2, respectively (p=0.97). OS rates of pts with active disease at SCT was 43%, 19% and 0%, respectively (p=0.01) suggesting an advantage for more intense regimens in this setting. Relapse rates were higher after RIC/RTC than MAC throughout the follow-up period. The rate was 30% and 18%, 1 year after SCT (p=0.03), 37% and 20% after 2 years (p=0.08), 49% and 27% after 5 years (p=0.02) and 51% and 29% after 10 years (p=0.02), respectively. NRM rates were higher after MAC than RIC/RTC in the initial 2 years after SCT but approached each other in the late post SCT course. NRM rate was 22% and 9%, 1 year after SCT (p=0.05), 22 and 10% after 2 years (p=0.08), 22% and 15% after 5 years (p=0.27), and 27% and 19% after 10 years (p=0.35), respectively. Thus, OS was similar within the first 2 years after SCT, 56% and 52% after MAC and RIC/RTC, respectively (p=0.86), but there was a trend for better OS after MAC later on, 51% and 36%, 5 years after SCT (p=0.26) and 44% and 31%, 10 years after SCT (p=0.22), respectively. Forty-seven pts were alive 5 years after SCT (42%). Nine of them died later on. Four of 24 RIC/RTC survivors at this point later died, 3 of second malignancies, 1 of relapse. Five of 23 MAC survivors at 5 years later died, 2 of relapse, 2 of chronic GVHD, 1 of MI. For pts surviving 5 years after SCT, the expected OS for the next 5 years was 86% and 87%, respectively (p=0.76). In conclusion, with a long-term follow-up of more than 10 years, RIC/RTC is an acceptable alternative to MAC in ineligible pts. NRM is lower after RIC/RTC in the early post SCT period, but late NRM negates this early advantage. Relapse rates are higher after RIC/RTC throughout the course. Due to these observations, it seems an advantage of MAC may become apparent 5-10 years after SCT. Pts who are alive 5 years after SCT can expect similarly good further OS with both approaches. Long-term follow-up studies (beyond 10 years) are of significant importance when assessing SCT outcomes in general and RTC SCT in particular. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Allogeneic Transplantation in Multiple Myeloma—Does It Still Have a Place?

2020 ◽  
Vol 9 (7) ◽  
pp. 2180
Author(s):  
Gösta Gahrton ◽  
Simona Iacobelli ◽  
Laurent Garderet ◽  
Ibrahim Yakoub-Agha ◽  
Stefan Schönland
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Cell Therapies ◽  
Novel Drugs ◽  
Car T ◽  
Long Term Follow Up

Novel drugs have improved survival for patients with multiple myeloma in recent years. However, the disease is still fatal. Allogeneic stem cell transplantation (Allo) has proven to cure some patients with the disease, but its role is controversial due to relatively high transplant-related toxicity and mortality (nonrelapse mortality, NRM). Using nonmyeloablative reduced-intensity conditioning (RIC), both toxicity and NRM can be reduced, and RICAllo is, therefore, an option for subgroups of patients. Upfront tandem autologous/RICAllo (Auto/RICAllo) was shown to be superior to single Auto or tandem Auto/Auto in both progression-free (PFS) and overall survival (OS) in two prospective studies with long-term follow-up, while three similarly designed studies did not detect a difference. A recent update of pooled patient data from four of these studies showed significantly superior PFS and OS with Auto/RICAllo. Importantly, none of these studies showed inferior results with Auto/RICAllo in patients less than 70 years of age. Auto/RICAllo appears to overcome some poor risk cytogenetic markers. Encouraging results have also been seen in treatment of relapsed patients. Combining Allo with new proteasome inhibitors and immunomodulatory drugs may further improve results. Other encouraging new cell therapies such as with CAR T-cells, NK- and CAR NK-cells may well have a place in combination with RICAllo. Such studies are warranted.

scholarly journals Long-Term Follow-Up after Reduced-Intensity Conditioning and Stem Cell Transplantation for Childhood Nonmalignant Disorders

2016 ◽  
Vol 22 (8) ◽  
pp. 1467-1472 ◽  
Author(s):  
Lisa M. Madden ◽  
Robert J. Hayashi ◽  
Ka Wah Chan ◽  
Michael A. Pulsipher ◽  
Dorothea Douglas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Long Term Follow Up ◽  
Reduced Intensity

Reduced-Intensity Conditioning for Allograft (RICT) after Cytoreductive Autograft (ASCT) in Relapsed/Resistant Hodgkin’s Lymphoma (HL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3294-3294
Author(s):  
A. M. Carella ◽  
E. Todisco ◽  
L. Castagna ◽  
A. Santoro ◽  
G. Catania ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Complete Remission ◽  
Long Term Results ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
High Dose Therapy ◽  
Previous Therapy ◽  
Reduced Intensity

Abstract Reduced-intensity conditioning for transplant (RICT) aims to exploit graft vs lymphoma (GvLy) effects while reducing conditioning-related toxicity. Because GvLy responses might be insufficient when HL are bulky and lymphoma growth is rapid, we pionered that intensive cytoreduction prior to RICT may allow GvLy reaction to be exploited (Carella et al. JCO2000; 18:3918). Thirty-eight patients with relapsed (n=26) or refractory (n=12) HL underwent RICT from an HLA-identical sibling preceeded by ASCT. Previous therapy consisted of 2–6 lines. High-dose therapy with ASCT consisted of BEAM protocol (n=29) or melphalan 200 mg/m2 (n=9). RICT consisted of fludarabine-cyclophosphamide (n=30) or fludarabine-melphalan (n=8). The two groups had similar prognostic factors. The median time to neutrophils and platelets recovery was 10 days and 16 days, respectively. Chimerism studies indicated 100% donor-derived engraftment. Day 100 and cumulative (2 yrs) TRM were 5,3 % (2 pts) and 18% (7 pts), respectively. Seventeen patients (44%) are alive (12 in complete remission and 5 with stable disease) with a median follow-up of 41 months (7–110 months). Twenty-one patients expired (TRM n=7, disease progression n=14). In conclusion, tandem ASCT/RICT is feasible and effective salvage therapy for patients with advanced HL. The long-term results obtained appear encouraging.

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