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.

Unrelated Cord Blood Transplantation Using Myeloablative Regimen for Acute Leukemia Patients Aged between 50 and 55 Years: Single Institutional Retrospective Comparison with Patients Less Than 50 Years of Age.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2013-2013
Author(s):  
Takaaki Konuma ◽  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Older Patients ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Age Groups ◽  
Younger Patients ◽  
Cell Dose ◽  
Significant Difference

Abstract Background: Increasing age has been well-known as an obvious risk factor for graft-versus-host disease (GVHD) and transplant-related mortality (TRM) resulting negative impact on allogeneic transplantation including cord blood transplant (CBT). The incidence of sever GVHD after CBT, on the other hand, is lower than that after transplants using graft from adult cells, so we have expected the better results of CBT in older patients. Objectives and Methods: This study aimed to evaluate safety and efficacy of CBT using myeloablative regimen for older patients with acute leukemia. Patients and Methods: We retrospectively compared outcomes of older patients with acute leukemia with younger adults in our institute. Nineteen elderly patients (median age 52, range 50–55) and 81 young patients (median 49, range 16–49) received myeloablative conditioning regimen including 12 Gy of total body irradiation. GVHD prophylaxis comprised cyclosporine with (N=96) or without (N=4) methotrexate. Results: Comparisons of characteristics in the 2 age groups showed similar distributions for weight, gender ratio, diagnosis [de novo acute myeloid leukemia (AML), myelodysplastic syndrome related secondary AML, or acute lymphoblastic leukemia], disease status at transplantation, total nucleated cell dose and CD34+ cell dose in the graft before cryopreservation and proportions of HLA and sex compatibility between donors and recipients. The median period of follow-up for survivors after CBT was 730 days for older group and 1331 days for younger group, respectively. Grade II to IV acute GVHD occurred in 10 of 17 evaluable older patients and 49 of 75 evaluable younger patients (P = 0.61), while no older patients, but 6 younger patients developed grade III to IV acute GVHD. Extensive-type chronic GVHD occurred in 4 of 15 evaluable older patients and 18 of 69 evaluable younger patients (P = 0.96), respectively. The cumulative incidence of TRM at 100 days was 5% versus 6% (P = 0.70), and of relapse at 3 years was 29% versus 20% (P = 0.33) and the estimated disease-free survival at 3 years was 67% and 71% (P = 0.53) for older or younger patients, respectively. There was no significant difference in GVHD, TRM, relapse, and DFS between 2 age groups. Conclusion: The use of cord blood as a stem cell source might contribute to be decreased in the incidence of acute and chronic GVHD resulting in decreased TRM in older patients. Our results suggest that myeloablative CBT might be as safe and effective in patients with acute leukemia aged between 50 and 55 years as in younger patients.

Outcome of Patients Aged ≥60 After Allogeneic Hematopoietec Cell Transplantation: Age Has No Impact on Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3540-3540 ◽  
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang A. Bethge
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Allogeneic Hct ◽  
Kaplan Meier ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 3540 Historically, allogeneic hematopoietic cell transplantation (HCT) has been offered only to patients with good performance status and below the age of 60. However, the peak incidence of most hematologic malignancies is above 60 years of age. The introduction of reduced intensity conditioning (RIC) regimens enabled successful allogeneic HCT in patients with considerable comorbidities and older than 60 years. The impact of age on outcome of allogeneic HCT in patients ≥60 years has not been evaluated extensively. We retrospectively analyzed 109 consecutive patients (f=43, m=66) aged≥60 who received allogeneic HCT 2000–2010 at our institution. Median age of the patients was 65 years (range, 60–76). Patients were grouped in two cohorts depending on age: group 1 aged 60–65 years (n=60, median age=63) and group 2 aged 66–76 years (n=49, median age=68). Diagnoses were acute leukemia (AML n=65, ALL n=1), myelodysplastic syndrome (n=14), osteomyelofibrosis (n=7), non-Hodgkin lymphoma (n=9), multiple myeloma (n=8), aplastic anemia (n=1), chronic myeloid leukemia (n=2) and chronic lymphatic leukemia (n=2). At time of HCT, 41 of the patients were in complete remission (CR), 68 in partial remission (PR) (group 1: CR 21, PR 39; group 2: CR 20, PR 29) and 18 patients had a preceding HCT, 14 in group 1. Conditioning regimens were grouped in high (TBI/Bu+Cy, n=5, all group 1), intermediate (FLAMSA, Flu/Mel/BCNU, n=28, group 1=11, group 2=17), low (FLU+alkylans, n=48, group 1=32, group 2=16) and minimal (2GyTBI/Flu, n=28, group 1=12, group 2=16) intensity. Intermediate intensity conditioning was particularly used for high risk patients in PR (25/28). 22 patients were transplanted from matched related (MRD), 46 from matched unrelated (MUD) and 41 from mismatched unrelated donors (MMUD). Kaplan-Meier-estimated 3-year overall survival (OS) was 45% for all patients, 32% for group 1 and 62%, for group 2, respectively (p=0.02), with more patients with high risk constellation in group 1. 3-year OS for patients transplanted with MUD was 57%, with MMUD 46% vs. with MRD 0% (p=0.01). Non-relapse-mortality was 28% for all patients, 40% in group 1 and 12% in group 2, probably due to the higher intensity in conditioning in group 1. The outcomes with intermediate, low and minimal intensity conditioning were comparable, while all patients after high intensity conditioning died. Table 1 describes Kaplan-Meier estimated 3-year-OS and statistical univariate analysis by log-rank test in the different subgroups. Table 1. 3-year OS (in%) All Group 1 Age 60–65 Group 2 Age 66–76 Remission CR 52 p=0.25 31 p=0.76 77 p=0.15 PR 40 32 50 Conditioning high 0 p=0.5 0 p=0.08 – p=0.38 intermediate 52 50 53 low 48 43 57 minimal 45 17 67 Donor MRD 0 p=0.01 0 p=0.06 73 p=0.45 MUD 57 53 65 MMUD 46 40 33 GVHD acute no 18 p=0.003 13 p=0.008 33 p=0.27 ≥II 43 53 58 chronic no 39 p=0.25 36 p=0.70 52 p=0.08 limited 52 30 100 extensive 50 30 67 In group 1 the outcome of minimal conditioning was inferior compared to intermediate and low conditioning while patients in group 2 had a better outcome with minimal vs. low and intermediate conditioning. Incidences of acute GVHD ≥II, limited and extensive chronic GVHD (cGVHD) were 10%, 28% and 13%, respectively. In group 1, acute GVHD ≥II occurred in 13% and cGVHD in 35%, in group 2 in 5% and 41% of the patients, respectively. Acute GVHD ≥II was associated with inferior outcome (3-year OS of 18% vs. 43%, p=0.003) while cGVHD had a positive impact on OS. In group 2 patients with limited cGVHD showed better 3-year OS than patients without cGVHD (67% vs. 52%, p=0.12). Age alone had no major impact on outcome of allogeneic HCT. Patients aged ≥60 seemed to benefit from the use of MUD rather than an older MRD. Chronic GVHD had a positive influence on survival. Our data indicate that the regimen used should be tailored to disease risk and patient performance status. Disclosures: No relevant conflicts of interest to declare.

The Results of Patients with b Thalassemia Major Undergoing Peripheral Blood Stem Cell From Alternative Donor: New Conditioning Regimen for Thalassemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3034-3034
Author(s):  
Chunfu Li
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Peripheral Blood Stem Cell ◽  
Conditioning Regimen ◽  
Blood Stem Cell ◽  
Cell Transplant ◽  
Sibling Donor ◽  
Significant Difference ◽  
Alternative Donor

Abstract Abstract 3034 Background: Hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for thalassemia patients, However, most candidates for HSCT do not have a suitable family donor. In order to evaluate whether HSCT from an HLA–well -matched alternative donor can offer a probability of cure comparable to that of HSCT from sibling donor. The new conditioning regimen and peripheral blood stem cell transplant (PBSCT) from alternative donor (NF-08-thalassemia protocol) were used for b thalassemia patients. The improved outcome was summarized here. Objective: To evaluate the overall survival (OS), thalassemia-free survival (TFS), rejection (RE) and transplant related mortality (TRM) of NF-08-thalassemia protocol. Patients and Methods: Sixty-one thalassemia patients, 42 male and 19 female (median age, 7 years; age range, 3–15 years), were transplanted from 56 (32 patients were 8/8 and 24 patients 7/8 locus matched at HLA-A, B, Cw and DRB1) unrelated and 5 (1 patient 8/8 and 4 patients 7/8 antigen matched) parents donors from Oct.2008 to Jan.2011(median follow-up time, 14 months; range, 6–31months). NF-08-thalassemia protocol included Cyclosphosphamide (d-10 to d-9), Busulfan (d-7 to d-5), Thiotepa (d-4), Fludarabine (d-8 to d-4) and ATG (d-3 to d-1). PBSCs from unrelated (56 cases) and parents (5 cases) donor were used as only source of stem cells in all patients. GVHD prophylaxis included Cs A, MMF and sMTX. Results: OS, DFS and TRM in the cohort of 61 patients were 91.8%, 90.2% and 8.2%, respectively. Only one rejected his graft two months after transplantation. Acute GVHD III∼IV was 8.2% (5 patients) and none suffered from extensive chronic GVHD. Three patients died of acute GVHD and two died of the infection after transplantation. Discussion: In comparing this alternative donor HSCT with sibling donor HSCT (30 patients, using the same protocol, meanwhile), OS, TFS, RE and TRM were 91.8% vs. 85.9% (P=0.401), 90.2% vs. 79.2% (p=0.147), 1.6% vs. 6.9% (p=0.197) and 8.2%vs.14.1%, respectively. No significant difference was found. Summary: The results of alternative donor HSCT for b thalassemia patients are comparable with sibling donor transplant with using NF-08-thalassemia protocol. Disclosures: Li: Qi fa Liu: Workmates.

Complementary Transplantation with Haploidentical Stem Cells and Unrelated Cord Blood for Leukemia and Thalassemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1235-1235
Author(s):  
Chunfu Li ◽  
Yuelin He ◽  
Xuedong Wu ◽  
Xiaoqin Feng ◽  
Jianyun Liao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Mixed Chimerism ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Unrelated Cord Blood ◽  
Kinetics Of

Abstract Background Unrelated Cord Blood (UCB) Transplantation is a potentially curative therapy for leukemia and thalassemia; however, engraftment failure and slow immune reconstitution remain key clinical issues. We hypothesized that complementary transplantation (CT) of UCB with haploidentical stem cell graft (hap-SC) tolerized with post-transplant cyclophosphamide would result in rapid engraftment and low relapse rate without additional risk of graft-versus-host disease (GVHD). Therefore, we developed a novel complementary transplant approach. Patients and Method Sixty-six patients received CT between December 2012 and June 2016. Of them, 30 patients had malignance diseases (MD), including 11 lymphoid and 19 myeloid diseases, and 36 had thalassemia major (TM). Median age was 12 (range; 2-13) and 8 (3-17) years in the MD and TM group, respectively. Median follow-up time was 13 (7-32) and 19 (2-25) months, respectively. Conditioning (Regimen CT-13) included Cyclophosphamide on day-8 to -7, Busulfan on day-6 to -4, Fludarabine on day-6 to -2 and Thiotepa on day-3. Hap-SC was infused on day 0. GVHD prophylaxis consisted of Cyclophosphamide on day+3 to +4. UCB was infused on Day+6. Mycophenolate mofetil and Tacrolimuswas started on day+6 for GVHD prophylaxis. For 26 TM patients transplanted since 2014, they received identical regimen except with the additional Thymoglobulin on day -11 to -9 (Regimen CT-14). Results The chimerism status at last follow-up was Hap-SC, UCB, mixed stem cells (MSC) and rejection in 20, 9, 1 and 0 patient in the MD group; and 16, 14, 3 and 3 patients in the TM group. Interesting, the initial chimerism on day+28 in the TM group was Hap-SC, UCB and MSC engrafted in 15, 7 and 12 patients, respectively. Thus, the MSC was not stable in TM patients; UCB typically became dominant overtime instead of the initial majority from hap-SC (Fig. 1). In the MD group, the time to neutrophil >= 0.5x109/L, platelet >=20 x109/L and hemoglobin >=80 g/L was day+18 (14-36), +10.0 (6-51) and +7 (1-20) in the final hap-SC engrafted group; and+30 (22-35), +25 (1-64) and +7 (3-28) in the final UCB engrafted group. Overall survive (OS), disease-free survive (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were 75.6%, 64.3%, 24.7£¥ and 13.7%, respectively, in all 30 MD patients; and 79.3%,73.8%,15.5% and 12.3% (Fig.2), respectively, in the 25 cases with complete remission (CR) at the time of transplantation. The corresponding data were 89% vs. 88.9%£¬65.0% vs. 77.8%£¬31.1 % vs.12.5% and 10.3% vs.11.1%£¨p>0.05 in all pairs), respectively, in hap-SC and UCB engrafted groups. Donor carrying KIR centromeric B motif was associated with reduced RI (10 % vs. 33.9%). In TM group, OS, thalassemia free survive (TFS), rejection and transplant-related mortality were 91.2%, 85.7%, 5.6% and 8.8%, respectively in all 36 patients. Impressively, all of the 26 patients who received the newer CT-14 protocol were alive without TM (Fig. 2). 7/10 UCB carrying KIR centromeric B motif engrafted. In the MD group, 23.3% had grade II-IV and10.0% had III-IV acute GVHD. Grade II, III and IV acute GVHD occurred in 3 patients, respectively, in TM group. One MD patient had severe chronic GVHD (lung) after DLI for relapse. No moderate chronic GVHD occurred in TM groups. Summary The CT-13 regimen resulted in high OS and DFS, especially in CR patients in the MD group. The CT-14 leaded to 100% TFS in thalassemia patients. Acute and chronic GVHD were acceptable. Donor carrying centromeric B motif promoted engraftment and reduced RI. A multicenter study should be developed in the future based on our favorable results. Figure 1. Kinetics of mixed chimerism in thalassemia patients Figure 1. Kinetics of mixed chimerism in thalassemia patients Figure 2. Results of malignance diseases in CR status at the time of transplant Figure 2. Results of malignance diseases in CR status at the time of transplant Figure 3. Thalassemia-free survive resulted from regimen CT-14 Figure 3. Thalassemia-free survive resulted from regimen CT-14 Disclosures No relevant conflicts of interest to declare.

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.

Cost effectiveness of G-CSF after allogeneic peripheral blood stem cell transplant.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18540-e18540
Author(s):  
Vijendra Singh ◽  
Seongho Kim ◽  
Hyejeong Jang ◽  
Asif Alavi ◽  
Divaya Bhutani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hospital Stay ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Allogeneic Pbsct ◽  
Significant Difference ◽  
Neutrophil Engraftment

e18540 Background: In spite of the fact G-CSF has been used post stem cell transplant (SCT) to accelerate neutrophil engraftment its use post allogeneic SCT remains controversial. ASCO does not recommend its use after allogeneic SCT. To further evaluate the effectiveness of its use, we compared outcomes in pts who underwent related and unrelated peripheral blood SCT(PBSCT) either with or without the use of G-CSF post SCT. Methods: This is a retrospective study comparing early outcomes in pts who received G-CSF starting on day + 6 post SCT until engraftment with pts who did not receive a planned course of G-CSF. Pts who underwent Allogeneic PBSCT between 2012-2014 at our institution were included. Pts who received marrow, haploidentical or cord blood transplants were excluded. Associations with survival outcomes were assessed by univariable and multivariable Cox proportional regression models. Results: A total of 162 patients were evaluated. Sixty-five pts received G-CSF post SCT and 97 did not. The only difference between the two groups was that more pts in the G-CSF group received myeloablative-conditioning (MAC) regimen (78% vs. 55%, p = 0.008). Other pt characteristics were not significantly different. Length of hospital stay was significantly lower in the G-CSF group (24 vs. 27 days P = 0.002). Pts who received G-CSF had earlier neutrophil engraftment (median, days 11 vs. 14 p = < 0.001). The median day of platelet engraftment was 15 days in both groups. There was no significant difference between the 2 groups in re-admissions in the first 100 days, and the incidence of acute or chronic GVHD. In multivariate analysis use of G-CSF did not significantly impact non- relapse mortality, relapse free survival and overall survival. However, relapse rate was significantly lower in G-CSF group in multivariable analysis (hazards ratio = 0.44, p = 0.03). Conclusions: Use of G-CSF post allogeneic PBSCT is associated with earlier neutrophil engraftment, shorter hospital stay and a suggestion of a reduced relapse rate after PBSCT. Our experience suggests that use of G-CSF (on average for approximately 5 days) in this setting is cost effective as it reduces hospitalization duration without adversely impacting post-transplant outcomes.

Novel Conditioning Regimen for Haploidentical Hematopoietic Cell Transplant for Severe Aplastic Anemia in Children

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5651-5651 ◽  
Author(s):  
Hasan Hashem ◽  
Rawad Rihani ◽  
Eman Khattab ◽  
Mayada Abu Shanap ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Stem Cell Source ◽  
Cell Source

New hematopoietic cell transplant (HCT) approaches are urgently needed for patients with severe aplastic anemia (SAA) who lack an HLA-identical donor. Haploidentical HCT with post transplant cyclophosphamide (PTCy) represent a potential universal available option for almost all children with SAA. We present a novel conditioning regimen for haploidentical HCT in children with SAA in a center where horse ATG is not available. Conditioning regimen consists of rabbit ATG 2.5 mg/kg/day from day -9 to -7, Fludarabine 30 mg/kg/day from day -6 to -2, Cyclophosphamide 14.5 mg/kg/day from day -6 to -5, Thiotepa 5 mg/kg/day from day -4 to -3, and 4 Gy TBI on day -1 in in two fractions. GvHD prophylaxis consist of PTCy 50 mg/kg/day on days +3 and +4 along with Cyclosporine A and Mycophenolate mofetil (MMF) starting on day +5. Four consecutive children with SAA referred to our center for haploidentical HCT starting in 2018. Median age at HCT was 9 years (5-16) with 3 males and 1 female. All patients were heavily transfused with both blood and platelets prior to referral for HCT. Two patients had strong and one had weak positive anti-HLA antibodies (DSAs) and received desensitization with IVIG, Rituximab and plasmapheresis. One patient received buffy coat infusion on day -1 due to persistent strong DSAs despite desensitization. Median CD34+ dose received was 12 x 10e6, and median CD3+ dose was 29 x 10e6. Donors were all same blood group to patients. All patients successfully engrafted neutrophils at median of 13 days (12-14). Platelets engraftment in 3/4 patients at median of 7 days (5-10). All patients received peripheral blood as stem cell source. Three of four patients survived and doing well at last follow up. One patient had toxic death on day +38 due to chemotherapy related toxicity causing multi-organ failure. Chimerism analysis was full donor in all four patients at median follow up time of 11 months (2-12). Patients were sent home at median of 24 days post HCT. None developed grade 2-4 acute GvHD nor chronic GvHD. Acute GvHD of skin grade 1 stage 1 developed in 2 patient and managed with topical steroids. Viral reactivations consisted of CMV viremia and BK hemorrhagic cystitis in all patients, and have all resolved. No post transplant autoimmune complications. Haploidentical HCT with PTCy represents a quick and first line approach in heavily transfused children with SAA. Although yet limited number of patients, this regimen is feasible and appears to be safe. A great advantage of this regimen is the rapid engraftment of both neutrophils and platelets. Moreover, although using peripheral blood as a stem cell source, there was no severe acute or chronic GvHD. Disclosures No relevant conflicts of interest to declare.

Does Donor Epstein-Barr Virus (EBV) Seropositivity Affect Recipient's Risk of Graft Versus Host Disease (GVHD) in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5766-5766
Author(s):  
Erden Atilla ◽  
Esmanur Kaplan ◽  
Pinar Ataca Atilla ◽  
Selami Kocak Toprak ◽  
Pervin Topcuoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction: EBV seropositivity in general population is 80%. Reactivation of latent infection in pre-transplant seropositive patients causes post-transplant lenfoproliferative disease (PTLD) following Allo-HSCT. The effect of donor EBV positivity on recipient's risk of graft versus host disease is not clear. Our aim is to present EBV seroprevalence and PTLD incidence as well as demonstrating the relation of EBV seropositivity with GVHD. Patients and Methods: A total of 364 allogeneic stem cell transplant recipients and donors were evaluated retrospectively from 2006 to 2015. During Allo-HSCT preparation procedures all recipients and donors were serologically tested. EBV specific IgG (VCA-IgG, EBNAIgG, EA-IgG) and IgM (VCA-IgM) antibodies were determined by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). All patients were followed for reactivation. Results: EBV IgG positivity was detected in 338 of recipients (92.8%) and 283 of donors (77.7%). There was no statistically difference detected between related or unrelated transplants. The mean age was 37 (range 16-67). 217 recipients were male (60%). 295 (81%) patients were transplanted for malign hematological diseases. The majority of patients were grafted from full-matched related donors (258, 71%). The most common source of stem cell was peripheral blood in 299 patients (82%) followed by bone-marrow in 56 patients (15%), bone-marrow plus peripheral blood in 9 patients (3%). 273 (75%) patients received myeloablative conditioning regimen. All patients received prophylactic acyclovir (in related transplants 400mg 3 times daily, in un-related transplants 800mg 3 times daily) starting from conditioning and up to three months posttranplant period. One pretransplant seropositive 26 year-old aplastic anemia patient had PTLD with EBV IgM positivity within 3 months posttransplant. He received 4 cycles of rituximab and prednisolone and achieved complete response. Three patients had EBV IgM positivity in posttransplant 4, 9 and 24th months with symptoms of infectious mononucleosis. The seropositivity resolved without treatment. Acute GVHD developed in 223 patients (61%) whereas chronic GVHD was detected in 285 (78%) of patients. The incidence of acute GVHD was similar when donor was EBV seropositive compared to seronegative (78% vs 22%, p=0.72). Chronic GVHD incidence was similar between donor EBV seropositive group compared to seronegative group (80% vs 20%, P=0.199). Conclusion: EBV seropositivity is common detected in 92.8% of our allo-HSCT recipient cohort. Donor EBV status did not have an effect on developing acute or chronic GVHD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Children with Acute Leukemia Given Hematopoietic Stem Cell Transplantation (HSCT) from an HLA-Compatible Sibling, or an Unrelated Donor (UD) or an HLA-Haploidentical Relative after Alpha/Beta T-Cell Depletion Have a Comparable Outcome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 195-195 ◽  
Author(s):  
Alice Bertaina ◽  
Barbarella Lucarelli ◽  
Riccardo Masetti ◽  
Pietro Merli ◽  
Roberto Rondelli ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Leukemia ◽  
Treatment Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background: Allogeneic HSCT is a widely used treatment for children with acute leukemia (AL) either relapsed or at high risk of treatment failure. However, an HLA-identical sibling is available for only 20-25% of patients and an UD can be located in a suitable time only for a portion of the remaining population. HSCT from an HLA-haploidentical relative (haplo-HSCT) is now considered an alternative option, especially in view of the recent insights in graft manipulation. We recently developed a novel method of more selective T-cell depletion based on physical elimination of α/β T cells (ClinicalTrial.gov identifier: NCT01810120), shown to be effective for both preventing graft-versus-host disease (GvHD) and for conferring improved protection against infections in comparison to haplo-HSCT performed through the infusion of positively selected CD34+ cells. The initial results on 40 patients with AL were reported at the ASH Meeting in 2013 (Bertaina et al). We now present the comparison of the outcome of 80 children with AL given haplo-HSCT after α/β T-cell depletion (group 1) with that of patients transplanted from an HLA-identical sibling (group 2) or an UD (group 3) in the same time period. Patients and methods: All patients with AL were transplanted at the Bambino Gesù Children's Hospital in Rome, Italy, between December 2010 and September 2014; 80 patients were included in group 1, 41 in group 2 and 51 in group 3. Patients were offered α/β T-cell-depleted haplo-HSCT in the absence of suitable conventional donor (HLA identical sibling or 10/10 UD evaluated using high resolution typing) or if affected by rapidly progressive disease not permitting time to identify an UD. Clinical characteristics of patients assigned to the 3 groups and those of their donor are shown in Table1. All children were given a fully myeloablative regimen. No group 1 patient was given any post-transplantation GvHD prophylaxis, while patients of group 2 and 3 were given Cyclosporine-A and short-term methotrexate. Group 1 and 3 patients received ATG Fresenius® (4 mg/Kg/day) from day -5 to -3 for preventing both graft rejection and GvHD. Results: All group 2 and 3 patients had sustained engraftment of donor cells, while 1 of the 80 patients included in group 1 experienced primary graft failure and was rescued by haplo-HSCT from the other parent. The cumulative incidence (CI) of acute GvHD was 30%, 41% and 42%, respectively. Remarkably, all children of the group 1 who developed acute GvHD had a skin-only involvement, while 17% and 16.3% of those of group 2 and 3 had either gut or liver involvement (p&lt;0.001). The CI of chronic GvHD was significantly lower in group 1 children than in those of groups 2 and 3 (p=0.02, see also Figure 1-Panel A). None of the 4 group 1 patients experiencing chronic GvHD had the extensive form of the disease, while the CI of extensive chronic GvHD of group 2 and 3 was 8% and 14%, respectively (p=0.01). Four, 1 and 6 children of patients assigned in group 1, 2 and 3, respectively, died for transplant-related causes; the CI of transplantation-related mortality (TRM) in the 3 groups is shown in Figure 1-Panel B. Relapse was the main cause of treatment failure and occurred at a comparable CI in all the 3 groups (see also Panel C of Figure 1). The 3-year probability of Event-Free Survival (EFS) was comparable in the 3 groups (Figure 1 - Panel D). In multivariate analysis, a Total Body Irradiation (TBI)-containing regimen was the only variable favourably influencing EFS of group 1 children (hazard ratio 2.93, 95% Confidence Interval 1.24-6.95). No variable influenced EFS of group 2 and 3 patients. Conclusions: Overall, these data indicate that haplo-HSCT after α/β T-cell depletion is associated with a risk of TRM and leukemia recurrence comparable to that of transplantation from an HLA-identical sibling or an UD, this translating in a similar probability of EFS. In view of the low incidence of chronic GvHD, this transplant option has to be considered a competitive alternative for children with AL in need of an allograft. Table. Sibling (n=41) MUD (n=51) Haplo (n=80) Sex p=0.77 M 27 32 55 F 14 19 25 Age at Transplantation (years) 10.6 9.4 9.7 p=0.20 Disease p=0.23 ALL 34 35 56 AML 7 16 24 Disease status at Transplantation p=0.13 CR1 20 30 30 CR2 21 20 47 ≥CR3 0 1 3 CMV serology (Donor/Recipient) p=0.001 neg/neg 8 5 6 neg/pos 8 21 7 pos/neg 1 4 11 pos/pos 24 21 56 Source of Stem Cells p&lt;0.0001 BM 40 40 0 PBSC 1 11 80 Conditioning regimens p=0.10 TBI-based 26 29 60 non TBI-based 15 22 20 Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Allotransplantation with Reduced Intensity Conditioning Regimens Modified To Lessen Transplant-Related Mortality Is a Useful Treatment for High-Risk Myeloid Diseases.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5328-5328
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie L. Elkins ◽  
Cheryl L. Hardy ◽  
Joe C. Files
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Peripheral Blood ◽  
Conditioning Regimens ◽  
Group 3 ◽  
Group 2 ◽  
One Year ◽  
Reduced Intensity ◽  
Group 1

Abstract Our stem cell transplant program treats a spectrum of hematologic malignancies that includes a number of patients with high risk myeloid disease. These challenging patients have lead our adult allotransplant program to employ alternative approaches to standard conditioning over the last three years using reduced intensity conditioning. The regimens are amenable to modification, allowing a goal of maximizing length of remission or period of low tumor burden while minimizing transplant-related mortality. We have conducted a retrospective study of patients receiving modified reduced intensity regimens of fludarabine, melphalan and Campath. Incidence of relapse, survival, tempo of engraftment and incidence of grades I–II and III–IV acute GVHD were compared. Three modifications of the regimen were: fludarabine 30 mg/m2 x 5d, melphalan 140 mg/m2 x 1d, Campath 20 mg/d x 5 days (Group 1); fludarabine and melphalan the same and Campath 20 mg/d x 3d (Group 2); fludarabine and melphalan the same and Campath 20 mg/d x 1d (Group 3). Fifteen patients with a median age of 48, range 24 to 58 years, were in the study. Twelve patients had AML, two had CML and one had MDS. Six patients were in CR at time of transplant and nine had detectable tumor or disease. Patients were not randomized for a conditioning group but were transplanted in a consecutive fashion; seven patients were in Group 1, five patients in Group 2 and three patients in Group 3. Stem cell sources were related BM for four recipients, related peripheral blood for one, unrelated BM for four, unrelated peripheral blood for four, a combination of related BM and peripheral blood for one, and one cord blood. All patients received an adequate CD34+ cell dose and none of the products was manipulated. Match grade was 6/6 for 13 transplants, 5/6 for one and 4/6 for the cord blood transplant. GVHD prophylaxis was the same for all recipients (standard dose cyclosporine or tacrolimus and MMF) tapering after day 30. No failures to achieve a WBC graft, including the cord blood recipient, occurred. Neutrophils (ANC &gt;500/dl) engrafted at a median of day 13 (range 10 – 48 days). Median follow-up was seven months (range 1.5 – 30 months). Two patients in Group 1 had grade I aGVHD and one continued to chronic GVHD. One patient in Group 2 had grade II and one had grade III aGVHD. None in Group 3 had aGVHD. Relapse occurred in three patients in Group 1 and they received DLI immunotherapy; no relapse occurred in Group 2 or 3. Twelve patients survived to day 100; three from Groups 1 or 2 did not. Four were alive at one year and four others who are still alive have not reached the one year mark. Four of the seven patients who have died were from residual disease; the other three were from treatment-related toxicity within the first 100 days. Eight of 15 patients remain in follow-up. We conclude that the application of fludarabine, melphalan, Campath conditioning regimens has been successful in this high risk group of patients. The cell source from an unrelated or related donor does not impact outcomes. There was a very low incidence of toxicity related to aGVHD, no failure to engraft and no unexpected complications. Lastly, this regimen has allowed modification to enhance its tumoricidal properties to the extent that these patients with myeloid disease have experienced a low 20% incidence of relapse. We will continue to modify and expand the patient selection criteria to elderly (&lt; 70 years old) AML in remission.

Sign in / Sign up

Export Citation Format

Share Document