A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced-intensity conditioning

2018 ◽  
Vol 100 (4) ◽  
pp. 335-343 ◽  
Author(s):  
Masaya Okada ◽  
Taizo Tasaka ◽  
Kazuhiro Ikegame ◽  
Nobuyuki Aotsuka ◽  
Takeshi Kobayashi ◽  
...  
Keyword(s):  
Cord Blood ◽  
Phase Ii ◽  
Marrow Transplantation ◽  
Phase Ii Study ◽  
Reduced Intensity Conditioning ◽  
Multicenter Phase ◽  
Reduced Intensity

scholarly journals Intrabone Marrow Transplantation of Unwashed Cord Blood Using Reduced-Intensity Conditioning Treatment: A Phase I Study

2012 ◽  
Vol 18 (4) ◽  
pp. 633-639 ◽  
Author(s):  
Masaya Okada ◽  
Satoshi Yoshihara ◽  
Kyoko Taniguchi ◽  
Katsuji Kaida ◽  
Kazuhiro Ikegame ◽  
...  
Keyword(s):  
Phase I ◽  
Cord Blood ◽  
Marrow Transplantation ◽  
Phase I Study ◽  
Reduced Intensity Conditioning ◽  
Conditioning Treatment ◽  
Reduced Intensity

scholarly journals Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Claudio G. Brunstein ◽  
Ephraim J. Fuchs ◽  
Shelly L. Carter ◽  
Chatchada Karanes ◽  
Luciano J. Costa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Cumulative Incidence ◽  
Marrow Transplantation ◽  
Phase 2 ◽  
Reduced Intensity Conditioning ◽  
Alternative Donor ◽  
Related Donor ◽  
Reduced Intensity

Abstract The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).

scholarly journals A Phase I/II Study of Intrabone Marrow Transplantation of Cord Blood Using Reduced Intensity Conditioning

2016 ◽  
Vol 22 (3) ◽  
pp. S358
Author(s):  
Taizo Tasaka ◽  
Yoshiko Matsuhashi ◽  
Nobuyuki Aotsuka ◽  
Takeshi Kobayashi ◽  
Kazuteru Ohashi ◽  
...  
Keyword(s):  
Phase I ◽  
Cord Blood ◽  
Marrow Transplantation ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Allogeneic Stem Cell Transplantation From Matched Related Donor in Patients Over the Age of 55 Years: A Prospective Multicenter Phase II Study of a Reduced Intensity Conditioning Associating Fludarabin-IV Busulfan and Thymoglobulin

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1952-1952
Author(s):  
Didier Blaise ◽  
Mohamad Mohty ◽  
Noel Milpied ◽  
Anne Gaelle Lecorroller ◽  
Nathalie Fegueux ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase Ii ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Phase Ii Study ◽  
Reduced Intensity Conditioning ◽  
Karnofsky Score ◽  
Myeloablative Conditioning ◽  
Reduced Intensity

Abstract Abstract 1952 Reduced intensity conditioning (RIC) regimens has been developed with the aim to perform safer allogeneic (Allo) stem cell transplantation (SCT) in population previously discarded because of higher SCT-related mortality. In this regard, the age of 55 years has been a long-lasting threshold above which standard Allo-SCT prepared with myeloablative conditioning (MAC) has been of limited use. Since a decade we now know that RIC can be safely used in this population. The RIC intensity remains however an issue: the more intensive, the more toxic but the less intensive, the less effective. In this study we prospectively assess, in patients (pts) over 55 years, eligible for an matched sibling Allo-SCT, the impact of a RIC with Fludarabin (30 mg/m2/day (D-5 to D-1)), IV Busulfan (0.8 mg/kg × 4/day (D-4 to D-3)) and rabbit anti-Thymocyte globulin (ATG) (2.5 mg/kg/day (D-2 to D-1). This phase II study followed a one-step Fleming procedure aiming to detect a decrease in non-relapse mortality (NRM) of 20% (α=0.01; β=0.10) as compared to literature data using standard MAC. To achieve this goal, a minimum of 74 analyzable pts were necessary and the inclusion of 82 pts were scheduled to anticipate drop-off after inclusion. Eventually, from 03/07 to 06/10, 82 pts have been included in 9 centers, of which 79 have been transplanted. Median follow-up is 24 months (10–50). All grafts were PBSC from a HLA identical sibling. CSA (2 mg/kg) was started on day −2. Median age is 60 (55–70) and male/female ratio 47/32. Karnofsky score was 90 (60–90). Diagnoses: AML=32; MDS=13; ALL=6; NHL=10; MM=13; CLL=4; Waldenström=1); 54 pts were in CR (CR1=31; CR2=15; CR>2=8), 22 in PR or SD and 3 in PD after a median of 2 (1–7) lines of chemotherapy. All pts engrafted and 46 presented with aGVHD (Grade: 1 n=32; Grade 2: n=7; grade 3–4: n=6) for a 17% (10–23) cumulative incidence of G≥ 2 aGVHD. A total of 47 pts experienced cGVHD (Limited: N=28; extensive: N=19) at a median of 4.5 months (3–21) after transplant for a one year overall and extensive cumulative incidence of 57% (46–68) and 34% (25–45) respectively. 12 patients died from NRM. The 6 month and overall cumulative incidences of NRM were 5% (0–10) and 16% (9–23) respectively. Karnofsky score was not predictive of NRM. 25 patients relapsed at a median of 4.2 months (0.8–12) for a cumulative incidence of 32% (23–42). Relapse incidence differed according to disease pre-transplant status (9 of 46 CR1/CR2 vs. 16 of 33 beyond CR2 pts; p=0.008). Three year overall and disease-free survival probabilities were 59% (45–71) and 79% (67–87) respectively. Considering the CR1 AML population (N=21), median age was 61 years (56–70) and probabilities of NRM, relapse, OS and LFS were 14% (IC95=0–27), 14% (IC95=2-26XX), 72% (IC95=47–86) and 67%(IC95=43-83) respectively. Economical data covering transplant and first 18 month post-transplant periods have been prospectively collected and are under analysis. HRQL (Health Related Quality of Life) was assessed over a 1-year period with the EORTC QLQ-C30 questionnaire (Days −7, +80,+180,+360). The lowest functioning scores and highest symptom scores were experienced 80 days after transplantation. Thereafter the level of functioning and level of symptoms returned to baseline levels, which is reassuring in this population. This study presents prospective data in pts of 55 years and older and treated in a multicenter trial with RIC but not non-myeloablative CDT. Taking account patient characteristics, they first confirm that Allo-SCT is a valid option in this population. Second they prospectively put in light that in elderly people the use of RIC is associated with similar NRM than after non-myeloablative conditioning regimen. The use of two days of rabbit ATG is associated with a low GVHD-induced NRM without a high relapse risk. This is likely due to the good efficacy/toxicity balance achieved by combining IV Busulfan and ATG. Further refining of this association, by cautious tuning of the IV Busulfan dose, is under process in our program. Comprehensive phase II studies of this type, including economical and QOL data, have become a prerequisite prior to further more ambitious trials of novel modalities and strategies. Disclosures: Blaise: Laboratoire Pierre Fabre: Research Funding; Celgene: Research Funding.

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