Influence of recipient's Age On the Outcome of HLA-Matched Sibling Transplants in Adult Patients with Severe Aplastic Anemia Who Conditioned with Fludarabine-Based Regimen

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1921-1921 ◽  
Author(s):  
SeungHwan Shin ◽  
JaeHo Yoon ◽  
SeungAh Yahng ◽  
SungEun Lee ◽  
ByungSik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Aplastic Anemia ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Severe Aplastic Anemia ◽  
Age Group ◽  
Increased Risk ◽  
Significant Difference

Abstract Abstract 1921 Background: There is a controversy concerning upper age limit of recipient in allogeneic stem cell transplantation (allo-SCT) of severe aplastic anemia (SAA) because older patients have an increased risk of transplant-related mortality (TRM). Recently, a less toxic regimen comprising reduced dose of cyclophosphamide (CY), fludarabine (Flu), and ATG (Flu/CY/ATG) was introduced for conditioning the patients with SAA scheduled for HLA-identical sibling allo-SCT. We analyzed the outcome of these patients after conditioning with Flu/CY/ATG regimen according to recipient's age. Method: We analyzed 82 consecutive adult patients transplanted from March 2002 to June 2011, followed conditioning with CY (50 mg/kg/day × 2 days), Flu (30 mg/m2/day × 6 days), and ATG (2.5 mg/kg/day × 4 days). Results: The median age of patients was 39 years (range, 13–58 years). 29 (35.4%) patients were very SAA at the time of allo-SCT. Stem cell sources were bone marrow (BM, n=59), peripheral blood stem cell (PBSC, n=12), and BM+PBSC (CD34+ cell selection, n=11). The conditioning regimen was well tolerated, with low TRM (4.9%). Neutrophil engraftment was observed in all patients; the median time to engraftment of neutrophils and platelets was 12 and 17 days, respectively. The 100-day cumulative incidence (CI) of acute graft-versus-host disease (GVHD, grade °Ã2) was 3.7% and 2-year CI of chronic GVHD was 4.4%. With a median follow-up of 3 years, overall survival (OS) and failure-free survival was 93% and 83%, respectively. Seven patients (8.5%) developed delayed graft failure and 6 patients of them have successful durable engraftment after second allo-SCT without TRM. Seven patients died of veno-occlusive disease (n=1), cytomegalovirus pneumonia (n=2), sepsis (n=2), clonal evolution after allo-SCT (n=2, 1 acute myeloid leukemia and 1 myelodysplastic syndrome), respectively. 3-year probability of OS by age group were 88% at less than 20 years old (n=8), 97% at 20–39 (n=34), 92% at 40–49 (n=26), 86% at 50–59 (n=14). There is no significant difference in OS according to age group (p=0.426). Conclusion: These data indicate that the Flu/CY/ATG conditioning regimen is well tolerable with low TRM and CI of GVHD in all age group. Similar OS according to 4-divided age group suggest that patient's age more than 50 years old might be possible candidate for allo-SCT in SAA with Flu/CY/ATG conditioning regimen. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Tranplantation (allo-SCT) for Adult Patients with Active Refractory/Relapsed Hematological Malignancies: a Survey From the Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3456-3456
Author(s):  
Patrice Chevallier ◽  
Noel Milpied ◽  
Karin Bilger ◽  
Gérard Socié ◽  
Ibrahim Yakoub-Agha ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conflicts Of Interest ◽  
Phase 1 ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Best Supportive Care ◽  
Adult Patients ◽  
Peripheral Blood Stem Cells ◽  
Hematological Diseases

Abstract Abstract 3456 Patients with active refractory/relapsed hematological diseases have a very poor outcome. Best supportive care or investigational therapies in phase 1 trials are usually proposed to these patients. However, some previous data suggested that allo-SCT might be an efficient therapy even in the setting of chemorefractory disease, because long-term immune-mediated disease control can be achieved in some patients after allo-SCT. The aim of this study was to evaluate on a large series the outcome of adult patients with active refractory/relapsed hematological diseases at time of allo-SCT and to determine which sub-group would most benefit from such approach. Between 2005 and 2009, 861 patients with various hematological diseases (AML, n=323; ALL, n=43; MDS, n=129, CMML, n=12; MPS, n=110; CML, n=28; NHL, n=100; HL, n=40; myeloma, n=36; CLL, n=24; and other, n=16) were treated with allo-SCT, and reported to the SFGM-TC Registry. Per study criteria, all patients presented with active refractory or relapsed disease at time of transplant. This series included 517 males (60%) and 344 females (40%). The median age at transplant was 50 (range, 16–71) years. The median interval between diagnosis and transplant was 17 (range, 1–99) months. 32% of patients failed at least one prior SCT (Autologous or allogeneic prior to allo-SCT). 350 (41%) patients received allo-SCT from an HLA-matched sibling donor, while the remaining 59% received an allogeneic graft from a matched unrelated or mismatched donor. The stem cell source was mainly peripheral blood stem cells (n=617; 72%). Bone marrow was used in 139 patients (16%), and cord blood in 107 patients (12%). Myeloablative conditioning regimen was used in 328 patients (38%), and various reduced-intensity regimens were used in other cases (62%). With a median follow-up of 290 (range, 1–1854) days after allo-SCT, engraftment was observed in 88% of cases. Grade II-IV and grade III-IV acute GVHD occurred in 35% (n=301) and 17% (n=144) of patients, respectively. Chronic GVHD was observed in 185 patients (21%; limited: n=77; extensive: n=82; missing data: n=24). At last follow-up, 347 patients (40%) were still alive (of whom 297 were in CR; 86%). 246 patients (28.5%) died of disease progression, and 232 patients died of transplant-related causes (NRM: 27%). The Kaplan-Meier (KM) estimates of overall survival (OS) at one and 2 years were 39% (95%CI, 36–43%) and 31% (95%CI, 28–35%), respectively. Of note, in patients with lymphoma (n=140), OS at 1 and 2 years were 57% (95%CI, 48–66%) and 49% (95%CI, 40–58%) versus 36% (95%CI, 32–40%) and 27% (95%CI, 23–31%), respectively, in all other diagnoses (P=0.00004). In a Cox multivariate analysis accounting for relevant factors, a diagnosis of lymphoma (NHL or Hodgkin) was the most significant factor associated with improved survival (RR=1.68; 95%CI, 1.3–2.2; P=0.0001). Despite its retrospective nature and the inherent selection biases, in case of availability of suitable donor, this data support the use of allo-SCT in adult patients with active refractory/relapsed hematological diseases, especially in patients with lymphomas. Results are expected to be further improved with the advent of novel conditioning regimens and maintenance therapies after transplant that are currently tested as part of prospective studies. Disclosures: No relevant conflicts of interest to declare.

Different Approaches Of Allogeneic Stem Cell Transplantation For Acute Leukemias In Suzhou (China) Lead To Similar Outcome Compared With European Group For Blood and Marrow Transplantation (EBMT) Results: A Pair-Matched Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2131-2131
Author(s):  
Jia Chen ◽  
Yin Lu ◽  
Myriam Labopin ◽  
Depei Wu ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Multivariate Analyses ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Acute Leukemias ◽  
Significant Difference

Abstract The first affiliated hospital of Soochow University initiated a program of stem cell transplantation for hematological malignancies in 2001 and has done until December 2011 a total of 460 transplants. The EBMT presently handles a registry with information on more than 450 000 transplants including over 100 000 transplants for Acute Leukemias. In order to evaluate the outcome of patients transplanted in Suzhou and to compare it with results from the EBMT, we collected the necessary information on all patients transplanted in Suzhou and we did a pair matched analysis. In Suzhou, the patient population studied consisted of 382 first allografts (322 adults and 60 children less than 18 years old). There were 223 Acute Myelocytic Leukemias (AML), 148 Acute Lymphoblastic Leukemias (ALL) and 11 biphenotypic leukemias. The median age of the patients was 32 years (4-63). By cytogenetics, 9% of the patients were good risk, 57% intermediate risk and 34% poor risk. Molecular biology was not available. 286 patients were transplanted in first remission (CR1), 63 in CR2 and 30 in more advanced disease. Donors were identical siblings in 57%, unrelated in 30%, mismatched relatives in 13%. The source of stem cells was bone marrow (BM) (harvested after stimulation of the donor by GCSF) in 40%, Peripheral Blood (PB) in 36%, BM + PB in 17% , Cord Blood in 4% and other in 3%. 97% of the patients received myeloablative conditioning (MAC) with no Total Body Irradiation (TBI) in 76%, and 3% reduced intensity conditioning (RIC). 98% of the patients engrafted. Acute Graft versus Host Disease (aGVH) grade >=2 occurred in 43%. The cumulative incidence of chronic GVHD at 2 years was 26±2%. With a median follow up of 21 months (1-143), 2 year overall survival (OS), Leukemia free survival (LFS), Relapse Incidence (RI) and non Relapse Mortality (NRM) in patients allografted in CR1 were 76± 3, 65± 3, 18± 2 and 17 ± 2% and in CR2 52± 7, 36± 7, 37± 7 and 28 ± 6%. TBI in MAC was associated with poorer results (p< 0.01 for OS,LFS,RI). By multivariate analyses, The NRM was lower with PB (p=0.04) and PB+BM (p= 0.01) compared to BM and the OS higher ( p=0.05 and 0.01 respectively). In a pair matched analysis 246 adult patients from Suzhou transplanted in CR with BM and/or PB were matched with 484 patients from the ALWP EBMT registry. Matching factors were age, diagnosis (AML and ALL), disease status (CR1 or CR2), Cytogenetics and donor origin (identical siblings, unrelated, mismatched relatives). Patients from Suzhou were transplanted more recently ; the interval from diagnosis to transplant was shorter (138 days vs 154 days, p<0.0001). TBI was less frequently used for MAC both for AML and ALL (p< 0.0001 for each) and PB + BM was used in 17% of the cases versus 0% for EBMT (p < 0.0001). By univariate analyses the results were: Suzhou versus EBMT: OS 72 ± 3 vs 61 ±2 % (p= 0.05), LFS 62 ± 3 vs 55 ± 2% (p= 0.17), RI 19 ± 3 vs 22 ± 2% (p= 0.25), NRM 20 ± 3 vs 22 ± 2% (p = 0.67), incidence of chronic GVH 30± 3 vs 48 ± 2% (p< 0.0001). By multivariate analyses, there was no significant difference for OS (HR: 0.9 range 0.59-1.39), LFS (HR: 0.93, range 0.63-1.38), RI ( HR: 0.72, range 0.41-1.28) and NRM (HR: 1.21, range 0.70-2.10). We conclude that the results from Suzhou are identical to those obtained using the EBMT database, even though some approaches (GCSF stimulated BM, BM+PB, conditioning regimen) were different. Disclosures: No relevant conflicts of interest to declare.

Current Outcome Of HLA Identical Sibling Vs Unrelated DONOR Transplants In Severe Aplastic Anemia : An EBMT Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 707-707 ◽  
Author(s):  
Andrea Bacigalupo ◽  
Gérard Socié ◽  
Rose-Marie Hamljadi ◽  
Mahmoud Aljurf ◽  
A Mashan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Aplastic Anemia ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Treatment Strategies ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Cell Source ◽  
Risk Patients

Abstract Background Unrelated donor (UD) transplants for patients with acquired severe aplastic anemia (SAA) have been known to yield inferior results when compared to transplants from HLA identical siblings (SIB). With the significant improvement of UD transplants over the past decade, on may ask whether this is still true. Aim of the study To compare the outcome of UD with SIB transplants in recent cohort of patients reported to the European Group for Blood and Marrow Transplantation (EBMT) Aplastic Anemia Registry. Patients We have analyzed 1500 patients with acquired aplastic anemia (SAA), who received a first bone marrow (BM) or peripheral blood (PB),. HLA matched transplant between 2005 and 2009, from identical siblings (n=975) or unrelated donors (n=525). Excluded were cord blood grafts. Clinical characteristics of the two groups were different: although SIB vs UD grafts had comparable age (20 vs 21 years median age , p=0.1), SIB grafts were performed earlier (152 vs 607 median days from diagnosis, p<0.00001), had less frequently anti-thymocyte globulin (ATG) in the conditioning regimen (50% vs 61%, p<0.0001), had less frequently radiation based conditioning (5% vs 31%, p<0.00001), and more frequently received marrow as a stem cell source (61% vs 53%, p=0.002). Results The cumulative incidence (CI) of engraftment was 91% for both SIB and UD transplants; and the CI of acute GvHD grade II-IV was11% in SIB and 25% in UD grafts (p<0.0001). Infection was the leading cause of death (10% UD, 8% SIB), followed by GvHD (6% UD vs 3% SIB) and rejection (1,7% and 1,4% respectively). In multivariate COX analysis the strongest negative predictors of survival was the use of PB as a stem cell source (RR 2, p<0.00001), followed by patient age >20 years (RR 2.0, p<0.0001), an interval diagnosis-transplant (Dx-Tx) >180 days (RR 1.3, p=0.006) and no anti-thymocyte globulin (ATG) in the conditioning (RR 1.6, p=0.002). The use of an UD as compared to a SIB was not statistically significant (RR 1.2, p=0.4). When stratified for negative predictors, the actuarial 5 year survival of SIB and UD transplants was 91% vs 81% in low risk patients (n=541, 0-1 negative predictors, p=0.052), 74% vs 72% for the largest group of intermediate risk patients (n=829, 2-3 negative predictors, p=0.4) and 53% vs 50% for a small group of high risk patients (n=130, 4 negative predictors, p=0.8). Conclusions This study suggests that the outcome of UD and SIB transplant for SAA is currently comparable, if one corrects for confounding variables, and especially time to transplant. This information warrants the activation of an unrelated donor search for all patients lacking an HLA matched sibling, up to the age of 60, and this may be relevant for treatment strategies. Disclosures: No relevant conflicts of interest to declare.

Is Not Age, But Comorbidities. Allogeneic Hematopoietic Stem Cell Transplantation In Patients Older Than 50 Years In Argentina

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5467-5467
Author(s):  
Mariano Berro ◽  
Juan Garcia ◽  
Ana Basquiera ◽  
Maria Marta Rivas ◽  
Maria Cecilia Foncuberta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Significant Difference

Abstract Materials and Methods We retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplant (HSCT) in 9 centers from Argentina. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, source, conditioning and immunosupression. We analyzed the incidence and severity of acute Graft-vs-Host disease (aGVHD) with Chi Square, Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier and Relapse, Non Relapse Mortality y chronic GVHD (cGVHD) with CI. For multivariate analysis (MA) we included variables that in univariate had a p<0.2, used Cox regression model for time dependant outcomes and logistic regression for dichotomic variables, considering significant a p<0.05. Results Patients characteristics are listed in table 1. Between January 1997 and July 2013, 137 transplants were performed in adults older than 50 years, with a median follow up 1.3 years. Acute GVHD incidence was 41% (19% were grade II and 7.3% III-IV). The only variable associated with aGVH clinically significant (G II-IV) was AML that was protective (14% vs 35%, p<0.01; significant in MA, HR 0.29; 95% CI 0.12-0.72). Chronic GVHD incidence was 25%, extensive in 9.4% and the only risk factor for this outcome was MPN (1-3 years 40%-NA vs 12-20%, p=<0.01). Global OS 1 and 3 years was 44 and 20%, DFS was 33 and 20%, Relapse was 35 and 41% and NRM was 36 and 43% respectively. Co-morbid patients showed a significant increase in NRM (HCT.CI 0 vs 1 vs ≥2, 1-3 years 17-24%, 40-46% and 45-67%, p=0.01; significant in MA, for HCT.CI 0 vs ≥1, HR 2.4, 95% CI 1.12-5.25), as well as male patients (1-3 years 36-47% vs 23-27%, p=0.03), MPN (1-3 years 43-65% vs 29.34%, p=0.01) and Cyclosporine based immunosuppressant regimen (CSA) vs tacrolimus (1-3 years 47-53% vs 25-36%, p=0.01). AML patients experienced a higher relapse rate (1-3 years 50-50% vs 28-32%, p<0.01) as well as Fludarabine-Busulfan conditioning (1-3 years 45-48% vs 31-32%, p=0.02). Finally patients without comorbidities (HCT.CI 0 vs ≥1) had higher OS (1-3 years 54-30% vs 36-16%, p=0.03) and DFS (1-3 years 43-31% vs 30-15%, p=0.05) as well as tacrolimus vs CSA base regimen that had higher OS (1-3 years 49-25% vs 31-13%, p=0.01) and DFS (1-3 year 41-26% vs 20-11%, p<0.01; significant in MA, HR 0.56, 95% CI 0.33-0.98). Age (older than 60 vs younger), type of donor, use of myeloablative conditioning regimen and source did not showed any significant difference in the outcome analyzed. Conclusion HSCT is a valid therapeutic option for older patients. In this retrospective analysis of patients older than 50 years, we found that the main risk factors that impact in transplant outcome are patients comorbidities and not age, whereas transplant related toxicities increase with the number of comorbidities and therefore decrease OS and DFS. Beyond the fact that certain disease experienced more aGHVD (AML) or cGVHD and higher NRL (MPN) the other factor significantly related in transplant outcome was the use of tacrolimus vs CSA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reduced Intensity Conditioning for Haploidentical Transplantation Using Double Source of Hematopoietic Stem Cells and Post-Transplant Cyclophosphamide for Severe Aplastic Anemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5745-5745
Author(s):  
Ana Rojas Fonseca ◽  
Vivian Aparecida Zanao ◽  
Katya Parisio ◽  
José Salvador Rodrigues de Oliveira
Keyword(s):  
Aplastic Anemia ◽  
Conflicts Of Interest ◽  
Jc Virus ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Haploidentical Transplantation

Significant improvements in haploidentical stem cell transplantation (haplo-SCT) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for haplo-SCT for SAA remains undefined. A recent review demonstrated haplo-SCT using NMA and RIC, engraftment between 75 to100% and OS one year of 75-100%. In our Institutions we started a double source since Jan 2017 using a RIC protocol that is the objective of this presentation. There were nine haplo-SCT in eight patients in two Brazilian centers, Hospital Santa Marcelina (n=5) and Hospital São Paulo (n=3). All patients were male, median age 26 years old (14-39), nocturnal paroxysmal hemoglobinuria clonality in five (62,5%); treated with Cyclosporine, Thymoglobulin (n=4), Eltrombopag (n=1), Eculizumab (n=2) and/or Alemtuzumab (n=1). Median time disease to transplant was 15,7 months (3.8-192). All patients submitted more than 20 RBC transfusions, and median of ferritin was 2,283 ng/mL (753-3,486). One patient had carbapenem-resistant gram-negative bacilli (CRNGB: Escherichia coli, Klebsiella pneumoniae and/or Pseudomonas aeruginosa). Panel reactive antibody was negative in all patients. The donor was a sibling in 44% (n=4), father and mother 22% each (n=2) and one patient received cells from his cousin after an early failure of engraftment from mother first transplant. The cause of this failure was a JC virus and adenovirus acute infections. The second haplo-SCT conditioning was Fludarabine, Cyclophosphamide and 600 cGy TLI. There were seven male donors. RIC was consisted of Fludarabine, Cyclophosphamide and total body irradiation (TBI) 200 cGy. The source was G-CSF primed bone marrow (G-BM) grafts in combination with PBSC no ex-vivo T cells depleted, and Cyclophosphamide 50 mg/Kg/day IV on days +3 and +4 post-transplant (PTCy), as well as graft versus host disease (GvHD) prophylaxis. The median of G-BM MNCs was 5.4 x 10⁸/Kg (2.3-8.7), and PBSC was 10 x 10⁶CD34+/Kg (4-18.7). One (11%) patient died for sepsis at day +13, he was the only with a confirmed CRGNB colonization before transplant. The ANC recovery was at day +17 (13-24). No one had Sinusoidal Obstructive Syndrome. Acute GvHD grade II and moderate chronic GvHD was observed in two patients (25%). Two patients had engrafting failure: the first at day +30 and received a successfully new haplo-SCT; the second at day +60, with a partial donor reconstitution without dependence of transfusion after immunosuppressive therapy. These two patients had female donors. The OS and DFS at two years were 87.5% and 75%, respectively. In conclusion, with a median follow-up of 30 months, haplo-SCT, PTCy with double source keep the 87.5% overall survival, with no one severe chronic GvHD. Our data suggests an excellent results for haplo-SCT, PTCy, RIC, double source in the SAA treatment. However, prospective well-designed trials need to confirm these results. Disclosures No relevant conflicts of interest to declare.

Outcome of Allogeneic Stem Cell Transplantation for Patients with Severe Aplastic Anemia after Conditioning with Procarbazine, ATG and Cyclophosphamide: A Single Center Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2027-2027
Author(s):  
Ki Seong ◽  
Jong Wook Lee ◽  
Yoo Jin Kim ◽  
Hee Je Kim ◽  
Chang Ki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Platelet Recovery ◽  
Matched Sibling

Abstract Background: Cyclophosphamide (CY, 200 mg/kg) plus ATG seems to be accepted as a standard conditioning regimen in HLA-matched sibling stem cell transplantation (SCT) for severe aplastic anemia (SAA). We report herein the outcome of allogeneic SCT for the patients with SAA conditioned with procarbazine (PCB), ATG and CY. Methods: Between January 1995 and March 2004, consecutive one hundred and sixty two patients with SAA received matched sibling SCT after conditioning with PCB, ATG and CY. The median age of patients was 28.5 (16~50) and median interval between diagnosis and SCT was 10.5 months (1~216). Fifty-five patients (34%) had a history of immunosuppressive therapy before SCT. The conditioning regimen consisted of PCB (6.25 mg/kg/day, 6 days), CY (50 mg/kg/day, 4 days) and ATG (1.25 mg/kg/day, 3 days). No graft manipulation was performed in 92 patients (52%), and donor marrow expansion and megadose transplantation (bone marrow plus CD34+ isolated PB as a stem cell source) were done in 35 patients (21.6%). All patients received of cyclosporine and methotrexate as GVHD prophylaxis. Results: The median dose of CD34+ and CD3+ cells infused were 4.8 x 106/kg (0.8~49.6) and 5.1 x 107/kg (0 ~ 38), respectively. Median time to neutrophil recovery more than 500/μL and platelet recovery more than 20,000/μL were 13 days (0~49) and 19 days (0~150), respectively. All patients achieved successful primary engraftment, but delayed engraftment failure developed in 18 patients (11%). Ten among 18 patients who developed graft failure received second SCT, resulting survival of 9 patients. The incidence of acute (more than grade II) and chronic GVHD were 9.3% (n=15) and 13.0 % (n=21), respectively. DFS and overall survival (OS) at 6 years was also 90%. Factors influencing on DFS on univariate analysis were patient and donor’s age, development of acute and chronic GVHD, and times of pregnancy (over 2 times). Development of acute and chronic GVHD, and occurrence of rejection were factors that influence DFS on multivariate analysis. Causes of death (n=15) were pneumonia (n=4), rejection (n=4), GVHD±infection (n=2), chronic GVHD (n=1), MOF (n=1), CVA (n=1), autoimmune hemolytic anemia (n=1), and unknown (n=1). Conclusions: These data suggest that the conditioning regimen used in this study is feasible for patients with SAA who received matched sibling SCT. GVHD and rejection were the most important factors that influence DFS.

HLA-Haploidentical HSCT with Post-Transplant Cyclophosphamide for Severe Aplastic Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4510-4510
Author(s):  
Yuelin He ◽  
Chunfu Li ◽  
Xuedong Wu ◽  
Xiaohui Zhou ◽  
Xiaoqin Feng ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Donor Lymphocyte Infusion ◽  
Severe Aplastic Anemia ◽  
Platelet Recovery ◽  
Graft Versus Host

Abstract Abstract 4510 Objective To investigate the effect of pretransplantation donor lymphocyte infusion (DLI) and posttransplantation cycolphosphamide (CY) to prevent graft rejection and graft-versus-host disease (GVHD) after bone marrow transplantation plus peripheral blood stem cell transplantation from HLA-haploidentical mismatched related donors. Methods Four patients (median age, 11 years; range, 8–15 years) with severe aplastic anemia and all of them had HLA-haploidentical donors more than or equal to 2/8 HLA (HLA-A, B, C and DRB1) mismatched at antigen level. The conditioning regimen consisted of pretransplantation DLI (Lymphocytes, 1×10e7/kg at day -9); 40mg/m2/day of fludarabine (day-6 to -2); 3.2mg/kg/day of Busulfex (day-6 and -5); 10mg/kg/day of Thiotepa (day -4) and 50mg/kg/day of Cy on day -7, 14.5mg/kg on day-3,-2 and 40mg/kg on day +3,+4, respectively. The prophylaxis of acute GVHD consisted of tacrolimus and mycophenolate mofetil. The median follow-up time is 5 (rang: 3–6) months. Results The median times to neutrophil (>500/ÌL) and platelet recovery (>20,000/ÌL) were 21 and 23.5 days, respectively. No acute GVHD and Chronic GVHD were, so far, observed for all patients and were survive without SAA. Conclusion Posttransplantation cyclophosphamide for the prophylaxis of acute GVHD was safe and effective. Disclosures: No relevant conflicts of interest to declare.

Comparison of Outcomes Between Unrelated Donor and Sibling Donor Transplant in Adult Patients with Severe Aplastic Anemia: A Single Center Retrospective Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4151-4151
Author(s):  
Sung-Eun Lee ◽  
Jae-Ho Yoon ◽  
Seung-Hwan Shin ◽  
Seung-Ah Yahng ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Sibling Donor ◽  
Donor Transplant

Abstract Abstract 4151 For the patient with severe aplastic anemia (SAA) who do not have a sibling donor and had failed to immunosuppressive therapy, allogeneic stem cell transplantation (SCT) from an unrelated donor is therapeutic option. Although unrelated SCT (u-SCT) has shown less favorable outcomes, there were few studies comparing unrelated donor to sibling donor transplant. The aim of the present study was to evaluate the feasibility of u-SCT in adult SAA patients compared with sibling SCT (s-SCT). This study examined 157 consecutive patients who underwent allogeneic SCT at our institution between April 2001 and December 2011. In this study, for a homogenous cohort, patients who received second allogeneic SCT were excluded. The diagnosis of acute GVHD or chronic GVHD was made as the NIH published consensus criteria. There were 71 male and 86 female patients with a median age of 31 years (range, 13–59 years). The median interval from the diagnosis to transplantation was 24 months (range; 1–346 months). The median transfusions prior to SCT were 47 units (range; 4–680 units). Patients with SAA (n=114) or VSAA (n=43) had received SCT from sibling donor (n=82) or unrelated donor (n=75). The conditioning regimen for s-SCT consisted of fludarabine (180 mg/m2) + cyclophosphamide (CY, 100 mg/kg) + ATG (10 mg/kg), and the conditioning regimen for u-SCT consisted of TBI (fractionated, 800 cGy) + CY (100–120 mg/kg) ± ATG (2.5 mg/kg) (Lee JW, et al, Biol BMT 2011, 17:101). GVHD prophylaxis consisted of CsA + MTX in s-SCT and FK506 + mini-MTX in u-SCT, respectively. After a median follow-up of 45 and 50 months for s-SCT and u-SCT, respectively, the 3-year estimated OS rates were 92.7 and 89 % for s-SCT and u-SCT (P=0.650), respectively. 15 patients (7 in s-SCT, 8 in u-SCT) died of transplant toxicities, including in s-SCT, acute GVHD (n=1), infections (n=4), and occurrence of MDS or AML (n=2) and in u-SCT, acute GVHD (n=4), chronic GVHD (n=1), infection (n=1), thrombotic microangiopathy (n=1). Nine patients (8 in s-SCT, 1 in u-SCT) developed secondary engraftment failure. The cumulative incidence of acute GVHD (≥grade II) was 4.9% in s-SCT and 44.0% in u-SCT (P<0.001). The cumulative incidence of chronic GVHD also showed higher in u-SCT than s-SCT (4.2% vs 44.4%, P<0.001). This study showed that survival of u-SCT is comparable to that of s-SCT. Therefore, early application of u-SCT should be considered in patients with SAA/VSAA in case of availability of well matched donor. Because the incidence of GVHD is significantly higher in u-SCT than s-SCT, further study is mandatory to reduce the incidence of GVHD in u-SCT setting. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document