Reduced Intensity Conditioning Regimens with Alemtuzumab Result in Low Treatment-Related Mortality and Low Relapse Rate in Unrelated and Related Allotransplantation Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5253-5253
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie Elkins ◽  
Vincent Herrin ◽  
Cheryl L. Hardy ◽  
Joe Clark Files
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Relapse Rate ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Group 2 ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Group 1

Abstract From September, 2003, to July, 2006, 29 adult patients with hematological malignancies received reduced intensity conditioning (RIC) instead of standard conditioning for allogeneic transplant. The RIC regimens used in our program employ an ablative dose of melphalan and patients become cytopenic and transfusion-dependent. Patients were transplanted for a variety of malignancies including multiple myeloma, AML, CML, NHL, MDS, one renal cell carcinoma and one CLL. Eleven (38%) were in CR at time of transplant while 18 (62%) had relapsed or refractory disease. With a median follow-up of 8 mon (range 1–27 mon) we have completed a retrospective analysis of treatment-related mortality, d+100 and overall survival, engraftment, grades I-II and III-IV acute GVHD, and relapse rate. Two RIC regimens were used consecutively, consisting of either: fludarabine 30 mg/m2 × 5 d and melphalan 140 mg/m2 × 1 d in both groups, and Alemtuzumab 20 mg/d × 3d (Group 1) and × 2d (Group 2). Group 1 was 10 patients and Group 2 was 19. Median age was 53, range 24–66. Median age of Group 1 was 47 (range 24–59) and of Group 2 was 54 (range 34–66). Seventeen patients received MUD products (4 in Group 1 and 13 in Group 2) and twelve received MRD products. Cell source was bone marrow (8 patients), PBSC (18 patients) cord blood (2 patients) and combined products in 2 transplants (2 patients). All patients received an adequate C34+ cell dose or TNC dose (cord blood) and none of the products was manipulated. HLA matches were 6/6 antigen matches or better in Group 1 except for a 4/6 allele matched cord blood. All products were 6/6 or better in Group 2 except for two who were 8/10 allele matches, one 5/6 antigen match and a 4/6 serological match (cord). GVH prophylaxis was tacrolimus tapering after d+100 and MMF tapering after d+30. All patients except one achieved a WBC graft, and the ANC >500/dl occurred at a median of 12 d (range 10–48 d). The graft failure was a CML in Group 2 who received the 8/10 marrow product followed by a cord blood transplant that also failed. Eight (28%) of the cohort developed acute GVHD grades I-II (one from Group 1, 7 from Group 2) and two developed grades III-IV (one from each group). Five (17%) went on to develop chronic GVHD (one from Group 1, 4 from Group 2). Relapse or disease progression occurred in only 38% (4 in Group 1 and 7 in Group 2). Seven from the cohort were treated with one or more DLI to accelerate conversion to full chimerism and two from each group developed acute GVHD following the treatment. Incidence of treatment-related mortality by d+100 was low at 21%, with two patients in Group 1 and 4 in Group 2. Overall survival was 41%, 3 in Group 1 and 9 in Group 2. Most surprising was the overall survival of MUD patients, 41%, all from Group 2, which is higher than that reported by NMDP for unrelated transplants. In summary, we plan to continue accruing patients to both Alemtuzumab dosing regimens in order to compare the incidence of GVHD and relapse rate in each treatment arm. We conclude that a RIC regimen utilizing Alemtuzumab allows for a relatively low treatment-related mortality (21%), a low relapse rate (38%) and a superior survival (41%), especially in MUD transplants.

Comparative Analysis of Ablative and Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation in Treatment of Adult Patients with Chronic Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5414-5414
Author(s):  
Lidia Gil ◽  
Jan M. Zaucha ◽  
Jan Styczynski ◽  
Anna Czyz ◽  
Andrzej Hellmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Allogeneic Hsct ◽  
Sibling Donor ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Negative Outcome

Abstract Allogeneic HSCT remains the only curative therapy for chronic myelogenous leukemia (CML) patients. We compared results of myeloablative (MAB) and reduced intensity conditioning (RIC) HSCT from sibling donor in 62 pts with CML, treated between 2000 and 2005. In MAB group, 44 pts (median age 39.5, range 17–54 yrs) were conditioned with BuCy2 regimen. Thirty four pts were in chronic, 7 in acceleration and 3 in 2nd chronic phase. 26 pts received PBSC and 18 were grafted with bone marrow HSC. Transplanted material contained 3.8 (1.24–14.6) x 106/kg CD34+ cells. Prophylaxis of graft versus host disease (GVHD) consisted of cyclosporin (CsA) and methotrexate. Eighteen pts (median age 48, range 37–56 yrs) were treated with fludarabine-based RIC regimen. This group comprised 13 pts in chronic and 5 with accelerated phase. Patients were grafted with PBSC only, containing 4.75 (2.25–10) x 106/kg CD34+. CsA alone was given as GVHD prophylaxis. RIC group differ from MAB group by 2 factors: higher age (p<0.001) and higher EBMT pre-transplant (Gratwohl) risk score (p=0.028). Results: Hematopoietic recovery occurred in all pts in MAB group, and in 94% in RIC group. Probability of overall survival for all pts was OS=0.57±0.09. 31 pts developed acute GVHD ≥2 grade (21 in MAB and 10 in RIC) and 25 pts extensive chronic GVHD (18 in MAB and 7 in RIC). Mean survival, estimated 5-yrs OS, probabilities of GVHD incidence, relapse and treatment related mortality (TRM), estimated by Kaplan-Meier method, with respect to transplantation method, are shown in Table. TABLE: COMPARISON OF RESULTS IN MAB-HSCT AND RIC-HSCT Probability MAB-HSCT (n=44) RIC-HSCT (n=18) P Mean survival (years) 4.1 (95%CI=3.5–4.6) 2.1 (95%CI=1.1–3.0) Overall survival 0.78±0.07 0.24±0.13 0.0010 Relapse incidence 0.21±0.08 0.30±0.15 0.4069 Treatment related mortality 0.14±0.05 0.61±0.18 0.0108 Acute GVHD ≥ 2 0.51±0.08 0.64±0.12 0.9492 Chronic extensive GVHD 0.59±0.05 0.60±0.15 0.8344 Factors predicting negative outcome by Cox univariate analysis for all pts, were: AGVHD≥2 grade (p=0.0001, HR=2.78 95%CI=1.49–5.26), extensive CGVHD (p=0.0253, HR=3.83, 95%CI=1.01–14.6), female donor (p=0.0551, HR=1.54, 95%CI=0.99–2.40), pre-transplant risk score >2 (p=0.0053, HR=1.89, 95%CI=1.22–2.94) and RIC (p=0.0027, HR=1.96, 95%CI=1.26–3.03). Factors predicting negative outcome by multivariate analysis were: AGVHD≥2 (p=0.0001, HR=3.03, 95%CI=1.56–5.39), extensive CGVHD (p=0.0370, HR=2.75, 95%CI=1.17–6.49), pre-transplant risk score >2 (p=0.0507, HR=1.59, 95%CI=0.99–2.53) and RIC (p=0.0342, HR=1.64, 95%CI=1.17–6.49). Age >45 yrs did not predict for OS. In matched-pair analysis, identified by pre-transplant risk score and age, RIC group had lower OS (0.24±0.13 vs 0.88±0.08 p=0.0010), higher TRM (0.61±0.18 vs 0.06±0.05, p=0.0064), with no difference in AGVHD, CGVHD and relapse incidence, when compared to MAB group. In summary, this experience with sibling donor allogeneic HSCT in CML, demonstrates a similar incidence of AGVHD≥2 and extensive CGVHD in RIC and MAB groups, and more importantly, results of RIC-HSCT in adult CML are not satisfactory, mainly because of high treatment related mortality.

Less Treatment Related Mortality with Variable Intensity Conditioning Than Non-Myeloablative Conditioning in Unrelated and Related Adult Allogeneic Transplant Recipients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5051-5051
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie Elkins ◽  
Cheryl L. Hardy ◽  
Joe Clark Files
Keyword(s):  
Acute Gvhd ◽  
Transplant Recipients ◽  
Allogeneic Transplant ◽  
Myeloablative Conditioning ◽  
Variable Intensity ◽  
Group 2 ◽  
One Year ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Group 1

Abstract For the past four years our adult allogeneic transplant program has employed two alternative approaches to standard recipient conditioning, the use of non-myeloablative “mini” conditioning and variable intensity conditioning. We now report a retrospective comparison of relapse, day +100 and one year survival, engraftment and grades I-II and III-IV acute GVHD in unrelated as well as related recipients in these two preparative regimen groups. Patients with a variety of malignancies were not randomized to receive either non-myeloablative (Group 1) or variable intensity (Group 2) conditioning. Twenty patients with a median age of 49 (range 27–64, Group 1) and 17 patients also with a median age of 49 (range 24–58, Group 2) received either marrow or peripheral blood stem cells, usually with a 6/6 match grade; one recipient in Group 2 received a cord blood transplant (4/6 match). Group 1 regimen consisted of fludarabine 30 mg/m2 x 3d and TBI 200 cGY. Group 2 regimen consisted of Campath 20 mg/d either 5 or 3 days, fludarabine x 5d and melphalan 140 mg/m2 x 1d. GVHD prophylaxis was the same in both groups (standard dose cyclosporine or tacrolimus and MMF.) All patients received an adequate CD34+ cell dose and none of the products was manipulated. Relapse rate was 37% in Group 1 and 53% in Group 2. Day+100 survival and one year survival were 55% and 20%, respectively, in Group 1 vs 69% and 33% in Group 2. Only one patient in Group 2 had acute GVHD, grades I-II; none had grades III-IV. However, in Group 1, 6 patients had grades I-II and 8 had grades III-IV (40%). Graft failure occurred in five patients in Group 1, while no patients in Group 2 experienced it. We conclude, first, that in our program the application of variable intensity conditioning has been quite successful in unrelated transplant recipients, as well as in related. Second, significant treatment related mortality in the form of graft failure and acute GVHD occurred less frequently in recipients who received this conditioning than in those receiving non-myeloablative conditioning. This regimen requires some further modification to enhance its tumoricidal properties; however, its treatment-related toxicity is minimal and allows us to offer this therapy to patients with co-morbid conditions and older age.

Outcomes of 40 Adult Patients after Double Cord Blood Transplantation Using a Reduced Intensity Chemotherapy Conditioning Regimen.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 605-605
Author(s):  
Karen K. Ballen ◽  
Corey Cutler ◽  
Thomas R. Spitzer ◽  
Beow Yeap ◽  
Steve McAfee ◽  
...  
Keyword(s):  
Cord Blood ◽  
Total Dose ◽  
Aplastic Anemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cord Blood Unit ◽  
Reduced Intensity ◽  
Related Mortality

Abstract Umbilical cord blood is an alternative stem cell source for patients without matched related or unrelated donors. However, single cord blood unit transplantation in adults is associated with high transplant related mortality, mostly due to infection. In this study, we used a reduced intensity conditioning regimen followed by infusion of two partially matched cord blood units. The conditioning regimen was fludarabine 30mg/m2/day Days -8,-7,-6,-5,-4,-3 (total dose 180mg/m2), melphalan 100mg/m2/day Day -2, and rabbit antithymocyte globulin (thymoglobulin) 1.5 mg/kg/day Days -7,-5,-3,-1 (total dose 6.0 mg/kg). Cord blood units were a 4/6 or better HLA A, B, DR match with each other and with the patient, and contained a minimum combined pre-freeze cell dose of 3.7 x 107NC/kg. GVHD prophylaxis was cyclosporine and mycophenolate mofetil, for the first 21 patients, and tacrolimus and sirolimus for the second cohort of 19 patients. Forty patients, 22 males (55%) and 18 females (45%) with a median age of 48 years (range 19–64 years) were treated. The diagnoses were AML (n=14), ALL (n=1), NHL (n=10), CLL (n=2), MDS (n=5), Hodgkins Disease (n=5), aplastic anemia (n=2), and chronic myelogeneous leukemia (n=1). Thirty-five patients have greater than 100 days of follow-up and are included in this analysis. The cell doses infused were a median of 4.0 x 10 7NC/kg (range 3.0–6.7 x 107) and 1.9 x 10 5 CD34+ cells/kg (range 0.5–10.0 x 105). Two patients (both with MDS complicating aplastic anemia) experienced primary graft failure, and received second cord blood transplants using a different conditioning regimen. Among the remaining patients, the median time to an absolute neutrophil count >500 was 21 days (range 14–70 days). There were two late graft failures. The median time to a platelet count >20,000 unsupported was 43 days (range 21–125 days). The incidence of acute GVHD Grades II–IV was 40% for the patients receiving cyclosporine/MMF and 29% for patients receiving tacrolimus and sirolimus. There were no deaths from acute GVHD in the cyclosporine/MMF group and one death from acute GVHD in the tacrolimus/sirolimus group. Seven patients (20%) developed chronic GVHD. The 100-day transplant related mortality was 14%. Two deaths were related to Epstein Barr virus related lymphoproliferative disorder, and the other deaths were due to a CNS bleed, staphylococcal sepsis, and respiratory failure due to aspergillus infection. Two patients have relapsed and one has progressive disease. With a median follow up of 14 months (range 3–31 months) the overall survival is 74% and the disease-free survival is 67%. Chimerism analysis showed predominance of one cord by Day +100. In 71% of patients, the first cord blood unit infused predominated. In conclusion, engraftment of adult patients appears to be acceptable using double cord blood products and reduced intensity, non TBI conditioning regimen; the risk of serious acute and chronic GVHD is low, survival is excellent in a selected group of patients and relapse rate is low, suggesting preservation of graft versus leukemia effect despite the low T cell dose.

Myeloablative Conditioning Followed by T-Cell Depletion Is Associated with Low Treatment Related Mortality.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5221-5221
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas ◽  
Cecile du Toit ◽  
Andrew McDonald
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Disease Recurrence ◽  
Haematological Malignancies ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: Classically the conditioning for transplantation in haematological malignancies has been with myeloablative doses of radiation or chemotherapy, and was followed by variable immunosuppression for the prevention of GvHD. This strategy has been associated with substantial transplant related mortality from regimen toxicity and GvHD, which were most pronounced in older patients. Reduced intensity conditioning programs that are mainly immunosuppressive allow engraftment and predisposed to donor chimerism and appear to have lower TRM, but seem associated to higher rates of GvHD and disease recurrence. To better apportion conditioning strategies for patients undergoing allogeneic stem cell transplantation, we studied the outcome of 81 patients who received similar GvHD prophylaxis with T-cell depletion and immunosuppression, after myeloablative conditioning. Patients & methods: Patients with haematological malignancies, in remission or still responsive to chemotherapy who had an HLA identical sibling were offered T-cell depleted stem cell grafts. Conditioning was with ablative doses of either chemotherapy or total body radiotherapy. Stem cells were mobilised into the blood (PBPC) with G-CSF (5–10ug/kg × 5) and grafts were harvested by large volume (30 litres) apheresis. GvHD prophylaxis was by ex vivo depletion of lymphocytes from the graft with CAMPATH-1 H antibodies followed by therapeutic doses of cyclosporin until day 90. End points were TRM, disease recurrence rate and overall survival time. Results: 90 consecutive patients with median age of 45 (17–62) years were studied. The diagnosis included acute leukaemia (ALL in 7) in CR in 38, myeloproliferative disorders in 16, lymphoproliferative diseases in 26 and multiple myeloma in 10. Post transplantation, patients with CML received, in addition, escalating doses of lymphocytes at 6 months (maximum 1 × 107/kg CD3) or imatinib for 12 months. Median CD34+ cell number was 2.7 (1–12.3) and the median dose of campath-1H was 10 (range 7.5–45) mg. Median time to engraftment was 11 days. Overall, 20 (22%) individuals died while treatment related mortality occurred in 17% (n= 15; VOD 3, infections in 8, pneumonitis in 1, EBV lymphoma in 1 and GvHD in 2). GvHD (> grade1) occurred in 7 patients, was controlled with further immunosuppression but lead to death from infections in 6. Disease recurrence was seen in 12, but 7 with CML or myeloma responded to DLI. At a median follow up of 688 days, 77 survive; 75% in unsustained remission. Conclusions: Myeloablative conditioning is well tolerated in patients receiving T-cell depleted grafts, and treatment related mortality of <20% can be expected consistently with this strategy. This information is useful to more precisely select patients who would benefit most from reduced intensity conditioning schedules.

Addition of More Immunosuppressive Drugs As Graft-Versus-Host Disease (GVHD) Prophylaxis Does Not Improve Gvhd Outcomes in Reduced Intensity Allogeneic Hematopoietic Cell Transplantation from Unrelated Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5786-5786
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Fiorenza Barraco ◽  
Xavier Thomas ◽  
Marie Balsat ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Immunosuppressive Drugs ◽  
Advisory Committees ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Group 3 ◽  
Group 2 ◽  
Related Mortality ◽  
Group 1

Abstract Background: Reduced-intensity conditioning (RIC) regimens have led to a dramatic reduction of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The concept of RIC is to deliver adequate immunosuppression with manageable graft-versus-host disease (GVHD) and the eventual development of a potent graft-versus-leukemia effect. Nevertheless, GVHD prophylaxis remains a challenging task after allo-HSCT. While the combination of cyclosporine A (CsA) and a short course of methotrexate (Mtx) after transplantation is considered as the gold standard for GVHD prophylaxis after conventional myeloablative allo-HSCT from HLA-identical siblings, there is no consensus on the optimal preventive GVHD prophylaxis after RIC allo-HSCT. On the other hand, recent and ongoing studies are evaluating a promising GVHD prophylaxis strategy using post-transplantation cyclophosphamide (PTCy). The aim of this study is to evaluate the impact of different GVHD prophylaxis used after RIC allo-HSCT in patients receiving peripheral blood stem cells (PBSC) from unrelated donors for hematological malignancies. Patients and methods: We evaluated 127 consecutive patients with hematological malignancies who received RIC allo-HSCT and were followed in our center between January 2008 and January 2016; 74 (58%) were males, median age was 58 years (range: 18-70), 52 (41%) had acute myeloid leukemia, 36 (28%) myelodysplastic syndrome, 12 (10%) myeloproliferative syndrome, 9 (7%) Non-Hodgkin lymphoma, 9 (7%) chronic lymphocytic leukemia, 6 (5%) multiple myeloma and 3 (2%) chronic myeloid leukemia. At transplantation, 65 (51%) patients were in complete response (CR) or chronic phase (CP). RIC regimen consisted on fludarabine, intermediate doses of IV busulfan and anti-thymocyte golbulins (ATG) (Thymoblobulin) in 56 (44%) patients and a sequential FLAMSA regimen in 71 (56%) patients and who also received similar doses of ATG (Thymoglobulin). PBSC donors were 10/10 HLA matched in 81 (64%) patients and 9/10 HLA mismatched in 46 (36%) patients. Patients were divided according to GVHD prophylaxis into 3 groups: group 1 consisted on CsA alone with 23 (18%) patients, group 2 include patients who received either CsA + mycophenolate mofetil (MMF), n= 64 (50%) or CsA + Mtx, n= 20 (16%) or CsA + cyclophosphamide n= 5 (4%), and group 3 included patients receiving CsA + MMF + tacrolimus n= 15 (12%) patients. Results: After transplantation, all patients in group 1 engrafted after a median of 17 (3-25) days, 81/89 (91%) engrafted in group 2 after a median of 17 (5-58) days and 14/15 (94%) engrafted in group 3 after a median of 16 (9-24) days. We did not observe any significant impact of the type of GVHD prophylaxis on the 100-day incidence of grade II to IV acute GVHD, which occurred in 6/15 (40%), 34/81 (42%) and 7/14 (50%) for the groups 1, 2 and 3 respectively (p=0.18). Grade III-IV acute GVHD occurred in 3 (20%), 24 (29%) and 5 (33%) in the three groups respectively (p=0.11). Similarly, cumulative incidence of 1 year chronic GVHD was not different between groups 1, 2 and 3 reaching 46%, 43% and 46% respectively (p=0.6) among them 3/15 (20%), 18 (22%) and 3/14 (21%) patients had an extensive form. After a median follow-up of 22 months for surviving patients, although there was no significant difference between the three groups in terms of non-relapse mortality, we observed more infection-related mortality with 45% and 83% in groups 2 and 3 respectively compared to 47% in group 1. The cumulative incidence of relapse at 2 years was 22%, 31 and 26% for the three groups respectively (p=0.23). Overall survival rates at two years were 43%, 31% and 44 % for groups 1, 2 and 3 respectively (p=0.42). The multivariate analysis taking into account the type of disease, donor HLA matching, disease status at transplantation, type of RIC and the type of prophylaxis, showed that the incidence of acute GVHD was influenced only by the use of FLAMSA regimen from mismatched donors, HR= 2.2 [1.3-3.1], p=0.05 which had also the same impact on the occurrence of chronic GVHD. Conclusion: Despite its limitations and the need for prospective randomized studies, the results of our study suggest that in the RIC allo-HSCT from unrelated donors, the different GVHD prophylaxis associations lead to similar GVHD outcomes. Patients with more immunosuppressive drugs had a higher incidence of infection-related mortality and in which PTCy could be a better option. Disclosures Nicolini: BMS: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Complementary Transplantation Improved Results of Both Peripheral Blood Stem Cells and Unrelated Cord Blood Transplants in Thalassemia: A Multi-Center Study from China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4617-4617
Author(s):  
Chunfu Li ◽  
Sixi Liu ◽  
Yuelin He ◽  
Xiaodong Wang ◽  
Jianyun Liao ◽  
...  
Keyword(s):  
Cord Blood ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Ct Protocol ◽  
Significant Difference ◽  
Group 2 ◽  
Unrelated Cord Blood ◽  
Group 1

Background: Unrelated cord blood (UCB) transplant (UCBT) is not recommended in patients with thalassemia major (TM) so far. Post-transplant (PT) Cyclophosphamide (PTCy) with long pre-transplant immunosuppression therapy have improved haploidentical peripheral blood (PB) stem cell transplant (haplo-SCT) survival in TM patients but with 2/31 primary rejection. So, we designed a novel dual transplantation of UCBT following haplo-SCTwith PTCy(NF-14-TM-CT protocol). Aim:To improve results of haplo-SCT and UCBT in patients with TM. Patients and method: NF-14-TM -CT protocol was termed as double-insurance dual transplantsincluding a haplo-SCT and an UCBT, in which conditioning regimen consisted of ATG (at -10 to -8 day), Cy (-7), Fludarabine (-6 to -2), Busulfan (-6 to -4) Thiotepa (-3), haplo-PB (0), PTCy (+3, +4) and UCB (+6). PTCy serve as GVHD prophylaxes after haplo-SCT and as conditioning before UCBT. In total 131 patients with TM from three pediatric center in China received NF-14-TM-CT protocolfrom June, 2014 to April, 2019, with a median follow-up of 13 (2-59) months and a median age of 8 (3.5-17) years. Results Final haplo-PB engrafted(group1)in 76 patients with mean PBSC-MNCof 22.49 (±5.36) x108/kgand UCB nuclear cells (NC) of 5.95 (±3.39) x107/kg and final UCB engrafted (group 2) in 55 patients with mean PBSC-MNC of 21.78 (±5.68) x108/kg and mean UCB-NC of. 5.43 (±2.32) x107/kg. The 4-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR), and transplant related mortality (TRM) were 97.6%, 96.0%, 1.5%, and 2.4%, respectively (Fig. A), in total. The corresponding rates for group 1 were 98.3%, 96.9%, 1.7% and 1.8% and for group 2 were 95.5%, 93.8%, 4.5% and 1.4%, respectively. No statistic significant difference was found in OS, TFS, GR and TRM, respectively, when comparing group 1 with group 2 (Fig. B. C, D, E).The incidence of grade II-IV acute GVHD, III-IV acute GVHD, mild chronic GVHD, moderate/severe chronic GVHD, VOD, PT cystitisand PT hemolysis of the entire cohort was 16.8%, 6.87%, 9.92%, 1.52%, 4.60%, 31.3% and 14.5, respectively. Summary:Current study proved that the novel CT improved the results of haplo-SCT and UCBT in patients with TM. Disclosures Wing: Miltenyi Biotec: Employment.

scholarly journals Adult Umbilical Cord Blood Transplantation Using Myeloablative Total Body Irradiation, Fludarabine, and Thiotepa Conditioning

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3395-3395
Author(s):  
Sarah Anand ◽  
Samantha Thomas ◽  
Kelly Corbet ◽  
Cristina Gasparetto ◽  
Richard Lopez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Neutrophil Engraftment

Abstract Introduction: Umbilical cord blood (UCB) extends the curative potential of stem cell transplantation to adult patients without a suitable donor. The most commonly used myeloablative preparative regimen results in an unacceptably high 6-month treatment related mortality rate of approximately 32% (Barker J et al. Br J Haematol. 2015). In an attempt to reduce treatment related mortality, we piloted a modified myeloablative regimen with total body irradiation (TBI), fludarabine, and thiotepa. We report clinical outcomes from a cohort of patients who received single or double UCBT after conditioning with this regimen. Methods: Thirty-one consecutive adult patients ≥ 18 years old with hematologic malignancies who underwent single or double umbilical cord blood transplantation at Duke University from 2010 to 2015 were included in this study. The conditioning regimen consisted of thiotepa 5 mg/kg/day i.v. x 2 days (days -11 to -10), TBI 150 cGy twice a day for total nine fractions (1350 cGy days -9 to -5), and fludarabine 40 mg/m2/day i.v. x 4 days (days -5 to -2). Cord blood units were matched to the recipient at 4 or more HLA loci (intermediate-resolution for A and B, high-resolution for DRB1). Graft versus host disease (GVHD) prophylaxis was with tacrolimus (target level 10-15 ng/ml) and mycophenolate mofetil 1000 mg TID. Antimicrobial prophylaxis and supportive care measures including GCSF administration until ANC > 1000 were conducted per institutional protocol. Probabilities of neutrophil and platelet recovery, acute and chronic GVHD, and treatment-related mortality were estimated by the cumulative incidence method. Relapse-free and overall survival rates were estimated by the Kaplan-Meier method. Results: Thirty-one patients (median age 46 years; range, 19-65) with hematologic malignancies were evaluated. Twenty-four patients (77%) had acute leukemia or myelodysplastic syndrome, while 7 patients (23%) had non-Hodgkin's lymphoma or multiple myeloma. By the "Disease Risk Index" (Armand P et al. Blood. 2014), 20 patients (65%) had low or intermediate risk disease, while 11 patients (35%) had high or very high risk disease. 30 patients underwent double UCB and 1 patient received single UCB transplantation. The median cryopreserved total nucleated cell dose was 5.4 x 107/kg (range: 3.2-8.4 x 107/kg). The cumulative incidence of neutrophil engraftment was 90% (95% CI, 82%-99%; Figure 1) at a median time of 21 days (95% CI, 19-26). Three patients did not have neutrophil engraftment; two patients had early death at days 7 and 14 prior to engraftment, while one patient had graft failure requiring second transplant. The cumulative incidence of platelet engraftment was 86% (95% CI, 75%-97%) at a median time of 47 days (95% CI, 37-73). Cumulative incidences of grades II-IV and grades III-IV acute GVHD were 48% (95% CI, 34%-69%) and 10% (95% CI, 3%-28%), respectively. The overall incidence of chronic GVHD was 40% (95% CI, 27%-59%), with 17% (95% CI, 8%-37%) of patients experiencing moderate to severe chronic GVHD. Treatment-related mortality at 6 months was 13% (Figure 2), while at 1 year and 3 years was 27% and 33%, respectively. With a median follow-up of 35.5 months (95% CI, 12.7-52.2), disease-free and overall survival at 3 years was 51% (95% CI, 29%-69%) and 57% (95% CI, 36%-73%), respectively. Conclusion: UCB transplantation with the modified myeloablative conditioning regimen of TBI, fludarabine, and thiotepa results in reliable neutrophil engraftment with reduced early treatment related mortality as compared to standard myeloablative conditioning consisting of TBI, fludarabine, and cyclophosphamide. It provides a promising disease-free and overall survival in an older (median age 46), heterogeneous patient population. This regimen represents a reasonable alternative to standard conditioning with TBI, fludarabine, and cyclophosphamide and warrants further study. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Targeted immune depletion prior to reduced-intensity allogeneic stem cell transplantation results in rapid and complete donor chimerism with low treatment-related mortality

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6540-6540
Author(s):  
R. M. Dean ◽  
D. H. Fowler ◽  
S. M. Steinberg ◽  
J. Odom ◽  
J. Gea-Banacloche ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality

6540 Background: Significant variation in host immune status may influence outcomes after reduced-intensity (RI) allogeneic stem cell transplantation (alloSCT). We have investigated a strategy of targeted immune depletion (TID) with conventional chemotherapy to deplete host T cells and achieve a minimal disease state prior to RI alloSCT. The aim of TID is to rapidly establish complete donor chimerism after RI alloSCT in order to potentiate a graft-versus-tumor (GVT) effect. In a prospective phase II trial (NIH 03-C-0077), we evaluated the effect of TID on donor chimerism, acute graft-versus-host disease (GVHD), and clinical outcome. Methods: Thirty-one patients (pts) with relapsed and refractory hematologic malignancies (NHL = 16; HL = 4; CLL/PLL = 4; MDS/AML = 3; other = 4) were enrolled. Median age was 57 years (range: 31–71). All pts received EPOCH-F (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine) ± rituximab (R) as TID to deplete host CD4+ cells <100/μL. All pts then received a RI conditioning regimen consisting of fludarabine and cyclophosphamide followed by a T-cell replete allograft from HLA-matched siblings. GVHD prophylaxis consisted of cyclosporine plus short-course mini-methotrexate. Results: EPOCH-F(R) achieved the target host T-cell level in 74% of pts. All 31 pts engrafted after RI alloSCT. Complete donor chimerism (> 95%) was observed in 74% and 81% of pts at day +14 and +28 post-transplant, respectively. The incidence of grade II-III acute GVHD was 42% with no cases of grade IV acute GVHD. The median potential follow-up from transplant is 25 months. Actuarial treatment-related mortality at 1 and 2 years was 3% and 8%, respectively. Event-free survival probabilities at 1 and 2 years post-transplant are 65% and 49%, respectively. Ten pts are alive and event-free >24 months post-transplant. The overall survival probabilities at 1 and 2 years are 84% and 64%, respectively. Conclusions: TID prior to RI alloSCT results in rapid, complete donor engraftment and may potentiate GVT effects. This treatment strategy was associated with very low TRM and favorable outcomes in an older patient population with advanced hematologic malignancies. No significant financial relationships to disclose.

Analysis of 120 Pediatric Patients with Non-Malignant Disorders Transplanted Using Unrelated Plasma Depleted Cord Blood and the Role of Post-Thaw Wash

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4406-4406
Author(s):  
Joseph Rosenthal ◽  
Tang-Her Jaing ◽  
Lee Lee Chan ◽  
Gretchen Eames ◽  
Michael L. Graham ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Pediatric Patients ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Unrelated cord blood (UCB) is an important stem cell source for unrelated hematopoietic cell transplantation of patients with non-malignant disorders. Cell dosage is a critical factor for successful UCB hematopoietic stem cell transplantation (HSCT). The red cell reduced (RCR) and post-thaw wash techniques that are widely used incur significant nucleated cell loss. Three strategies were employed to maximize cell dose and improve outcome–use of cord blood processed with plasma depletion without red blood cell reduction (PD CB), avoidance of post-thaw wash, and the use of double cords (2X) when necessary. A CIBMTR-audited analysis was performed on all 120 pediatric patients with non-malignant disorders transplanted with PD CB at 29 U.S. and 17 international centers. Transplant characteristics: median age 3.5 years (range 0.1–14); median patient weight 15 kg (range 4–61); male 58%. The majority of patients (n=58; 55%) were Asian. Twenty-two (21%) patients were Hispanic, 15 (14%) were Caucasian, 6 (6%) were African-American, and three (3%) were of Middle Eastern background. HLA ABDR matches: 6/6–26; 5/6–48; 4/6–47; 3/6 or 2/6–6; median pre-freeze nucleated cell dose 10.5×107/kg; median pre-freeze CD34+ dose 3.7×105/kg; non-myeloablative regimen 24%; 58% infused without post-thaw wash (NW). Myeloid engraftment defined as ANC≥500 and 6-month platelet engraftment defined as ≥ 20K and ≥ 50K are 89±8%, 88±8%, and 84±6% respectively. The median time to myeloid and platelet engraftment are 21 days (range 11–64), 49 days (range 13–155), and 61.5 days (range 21–205) respectively. No major adverse event was observed in either the W or the NW group. The cumulative incidence of reported grade II–IV acute GVHD was 38±5%, and 19±4% had grade III–IV acute GVHD. 36±6% developed limited chronic GVHD, and 12±4% developed extensive chronic GVHD. With a median follow-up of 329 days (range 3–1928 days), the Kaplan-Meier estimates of 1-year TRM, OS and diseasefree survival were 20±6%, 88±6% and 72±6% respectively. Foregoing post-thaw wash for PD CB transplantation improved neutrophil (RR=1.75; p=0.01) and platelet engraftment (RR=1.72; p=0.02) and reduced TRM (RR=0.38; p=0.04). This series demonstrated that unrelated PD CB transplantation can be performed safely and effectively in children with life-threatening, non-malignant disorders. Additionally, the results demonstrate possible improvement in myeloid and platelet engraftment, overall and disease-free survival when post-thaw wash is not employed. Table 1. Summary of overall results Outcome All Patients N = 120 Washed CB N = 48 Unwashed CB N = 71 RR (Wash=Ref) P-value ANC500 Engraftment Cumulative Incidence Median # Days to Engraftment 87±6% d+21 86±9% d+25 89±8% d+19 1.75 0.01 Platelet 20K Engraftment Cumulative Incidence Median # Days to Engraftment 81±6% d+49 75±9% d+52 88±9% d+43 1.72 0.02 Autologous Recovery 3±2% 2±2% 4±3% 1.06 0.95 Acute GvHD II–IV Acute GvHD III–IV 38±5% 19±4% 31±7% 17±6% 45±7% 21±6% 1.74 1.38 0.11 0.50 Chronic GvHD Limited Chronic GvHD Extensive 36±6% 12±4% 14±6% 19±6% 60±10% 6±4% 5.69 0.24 &lt;0.001 0.08 Transplant-Related Mortality–100 Day Transplant-Related Mortality–3 Yr 10±3% 20±4% 11±5% 34±8% 9±4% 11±4% 0.38 0.04 Overall Survival–1 Yr Overall Survival–3 Yr 79±4% 79±4% 66±8% 66±8% 88±4% 88±4% 0.43 0.06 Disease-Free Survival–1 Yr Disease-Free Survival–3 Yr 72±5% 70±6% 58±9% 51±10% 84±5% 84±5% 0.48 0.07

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