scholarly journals Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up

2019 ◽  
Vol 25 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Erica Dahl Warlick ◽  
Todd E. DeFor ◽  
Nelli Bejanyan ◽  
Shernan Holtan ◽  
Margaret MacMillan ◽  
...  
Keyword(s):  
Hematologic Malignancies ◽  
Reduced Intensity Conditioning ◽  
Long Term Follow Up ◽  
Reduced Intensity

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 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 Regimen of Autologous Hematopoietic Stem Cell Transplantation±Mitoxantrone Consolidation In Multiple Sclerosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 372-372 ◽  
Author(s):  
Andrei A Novik ◽  
Aleksey N Kuznetsov ◽  
Vladimir Y Melnichenko ◽  
Denis A Fedorenko ◽  
Andrei V Kartashov ◽  
...  
Keyword(s):  
Clinical Response ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Long Term Follow Up ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Abstract 372 High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (ASCT) offers promising results in the treatment of multiple sclerosis (MS) patients. Reduced intensity conditioning regimens (mini-ASCT) is a way to improve the balance between benefits and side effects of this treatment approach. The goal of our research was to study the safety and treatment outcomes of mini-ASCT±Mitoxantrone consolidation in patients with various types of MS. 177 patients with MS: secondary progressive (SP) – 64 patients, primary progressive (PP) – 27, progressive-relapsing (PR) – 4 and relapsing-remitting (RR) – 82 were included in this study (mean age - 33.0, range: 17–54; male/female – 73/104). BM (BCNU 300 mg/m2, melphalan 50 mg/m2) was used as conditioning regimen. There were two treatments arms, with (n=55) and without (n=122) Mitoxantrone consolidation after mini-ASCT. The patients with unfavorable risk factors were included in consolidation therapy arm. Median EDSS at base-line was 4.0 (range 1.5 – 8.5). The median follow-up duration was 24.4 months (range 6 – 48 months). Neurological evaluation was performed at baseline, at discharge, at 3, 6, 9, 12 months after ASCT, and every 6 months thereafter. MRI examination was performed at baseline, at 6, 12 months, and at the end of follow-up. No transplant-related deaths were observed. In addition, there were no deaths in the study within all follow-up. The mobilization and transplantation procedures were well tolerated with no unpredictable severe adverse events. All 90 patients included in the analysis in the first arm, namely, those patients who did not receive consolidation therapy after mini-ASCT, responded to treatment. In 12 months post-transplant 43% patients improved, 50% – stabilized, and 7% – progressed. At long-term follow-up (mean 36 months), the clinical response in 48% patients was classified as an improvement; 43% patients remained stable. Two patients deteriorated to a worse score after 18 months of stabilization (SP MS and RR MS), and 2 others progressed after 24 months of improvement (PP MS and SP MS). Overall clinical response in this group was 82%. The vast majority of patients (96%) with RR MS were relapse-free. No active, new or enlarging MRI lesions were registered in patients without disease progression. Remarkably, all patients in this group who did not have disease progression were off therapy throughout the post-transplant period. The analysis of clinical outcomes in the second treatment arm with consolidation after mini-ASCT was performed in 41 patients. Notably, there was no disease progression registered in this group. In addition, there were no relapses in the patients with RR MS. At long-term follow-up (24 months) the majority of patients achieved clinical improvement (62.5%); others had disease stabilization (37.5%). In conclusion, this study provides ample evidence in support of safety and efficacy of reduced intensity conditioning regimen of ASCT in patients with various types of MS. Mini-ASCT without consolidation leads to overall clinical response in 82% of MS patients. Preliminary data on consolidation with Mitoxantrone after mini-ASCT show a real possibility to achieve a relapse- and progression - free period with the mean of 24 months (range 7–45 months) in 100% patients. Further studies should be done to validate conditioning regimens in MS patients undergoing mini-ASCT and to define a role of consolidation after transplantation. Disclosures: No relevant conflicts of interest to declare.

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