scholarly journals Updated Outcomes of NF-08-TM Protocol in HSCT for Patients with b-Thalassemia Major: A Large Prospective Study from Single Center

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2577-2577 ◽  
Author(s):  
Chunfu Li ◽  
Xuedong Wu ◽  
Yuelin He ◽  
Xiaoqin Feng ◽  
Jianyun Liao ◽  
...  
Keyword(s):  
Prospective Study ◽  
Conflicts Of Interest ◽  
White Cell Count ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Unrelated Donor ◽  
Donor Pool ◽  
Hematopoietic Stem ◽  
Curative Therapy ◽  
Donor Transplant

Abstract Background: The optimization of both erythrocyte transfusion and iron chelating has resulted in a remarkable improvement in the life expectancy of patients with thalassemia major (TM). However, only curative therapy remains allogeneic hematopoietic stem cell transplantation (HSCT). HLA matched sibling transplant (MST) has been commonly used for TM patients with well results. However, this option is unavailable to many patients as a result of a lack of compatible MS, especially in China. Matched unrelated-donor transplant (MUT) and Haploidentical-donor transplant (HIT) have be well performed in malignant disease. But in few thalassemia patients because of high risk of transplantation so far. To expand donor pool and to lower risk of HSCT from alterative donor, we designed a NF-08-TM protocol for MST, MUT and HIT for TM patients since 2009. Outcomes before June 2011 have published in “Blood” in 2012. Here we updated these outcomes. Aims: to check stability and reliability of NF-08-TM protocol in MST, MUT and HIT for thalassemia patients. Methods: 293 consecutive patients with TM underwent HSCT between January, 2009 and December, 2013 in our center, including 143 in MUT, 21 in HIT (≥ one HLA mismatch) and 105 in MST. Rate of male to female is 185:108. The median age at transplant was 6 years (rang:0.6-16), The median follow-up time is 29 months (range: 6-64). All patients received the NF-08-TM protocol, which included a new risk classification to adjust dose of IV Busulfex (Bu) and Cyclophosphamide (Cy), and a conditioning regimen of Bu following Cy instead of Cy following Bu. Simultaneously, a intensify graft versus host disease (GVHD) prophylaxis consisted of ATG, Cs A, MMF and short MTX was given. Results: The estimated 5-year overall survival and TM-free survival were 92.6%, 89.5% and 94.1%, and 90.5%, 89.5% and 92.2% in the MUT, HIT and MST, respectively. The cumulative incidence of graft rejection was 2.1% in total. The cumulative transplant-related mortality was 7.4%, 10.5% and 5.9%, respectively, in the MUT, HIT and MST. Incidence of cytopenia post-transplant (white cell count less than 3.0x109/L for 4 weeks or longer but CMV infection) was 20.6%. Conclusion: Our large sample prospective study provides results comparing MUT or HIT with the MST for TM patients, which showed that MUT or HIT was comparable with MST when using NF-08-TM-HSCT protocol. Disclosures No relevant conflicts of interest to declare.

Correlation Between Severity of cGvHD and Transplant Outcome: A Retrospective Monocenter Study Based on NIH Classification,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4088-4088
Author(s):  
Colombe Saillard ◽  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
Luca Castagna ◽  
...  
Keyword(s):  
Stem Cells ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Extensive Form ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Significant Difference

Abstract Abstract 4088 Background: Chronic graft-versus-host disease (cGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies is associated with lower relapse rate, due to graft-versus-tumor effect. We know that the extensive form is associated with higher transplant-related mortality after myeloablative conditioning regimen, mainly due to infectious complications as a consequence of immunosuppressive treatment. Beside the “classical” Seattle classification (limited or extensive form), a recent classification (from National Institute of Health, NIH) distinguishes three levels of severity: limited, moderate and severe. We compare here both classifications for patients receiving reduced-intensity conditioning (RIC) transplant and looked for any association of cGvHD severity with transplant outcome. Patients and Methods: We evaluated data on all adult patients with hematological lymphoid or myeloid malignancies who received HSCT from related or unrelated donor, using peripheral blood stem cells, after RIC regimens (with fludarabine-busulfan-ATG) between 1998 and 2010 at the Institut Paoli-Calmettes (Marseille, France). Data on main pre- and post-transplant variables were collected; cGvHD was classified according to its presentation and severity (with both Seattle and NIH classifications) and was correlated with overall survival (OS), non relapse mortality (NRM), and relapse. cGvHD was considered as time-dependent variable, and was included in uni- and multivariate models, after adjusting for age, disease risk, HLA compatibility, graft source and comorbidity score. Relapse or death before cGvHD was considered as a competing event. Results: 283 patients were evaluated, 121 have developed cGvHD (27 limited forms and 94 extensive forms), 162 have not, for an incidence rate of 10% and 33% of limited and extensive forms respectively. Median follow up was 607 days, patients had a median age of 50 years, transplanted for acute leukemia (55), lymphoma (78), multiple myeloma (49), myelodysplastic syndrome (24), CLL (12), CML (16) or others malignancies (19). Peripheral stem cells were mostly used (294 versus 20 bone marrow graft). We had 241 related donors and 77 unrelated donors. The median day of cGvHD occurrence was 132, we found 52 de novo forms, 40 quiescent and 26 progressive forms. After reclassification with NIH criteria, we obtained 28 mild, 52 moderate and 41 severe forms. 22 of 27 limited forms were classified as mild, the extensive forms were divided into 49 moderate and 39 severe forms. In multivariate analysis, mild and moderate forms were associated with better OS compared with other groups. Severe cGvHD was associated with significant increase in NRM. Among the other variables, only age was statistically significative in OS and NRM models. Although the incidence of relapse was lower in patients with cGvHD compared with those without, no significant difference was seen between the 3 groups of patients presenting it. Conclusion: Following a fludarabine-busulfan-ATG RIC, it seems that mild to moderate cGVHD forms are associated with better OS than patients without or with severe cGVHD. This is related to lower NRM than patients with severe cGVHD and at least a comparable antitumoral effect with respect to patients without cGVHD. This invites developing strategies limiting severity but not abrogating the effect of cGVHD. Disclosures: No relevant conflicts of interest to declare.

HLA and Kir Mismatch Transplant Affect Cytopenia Beyond Day 28 after Thalassemia Transplant: A Primary Manifestation of Chronic Graft Versus Host Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5929-5929
Author(s):  
Xiaohui Zhou ◽  
Chunfu Li ◽  
Jianyun Liao ◽  
Xiangjun Liu
Keyword(s):  
Conflicts Of Interest ◽  
Hla Class I ◽  
Thalassemia Major ◽  
Class I ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Hla Antibody ◽  
Cmv Status

Abstract Background Cytopenia beyond day 28 post-transplant (CB-28PT) following hematopoietic stem cell transplantation (HSCT) with β-thalassemia major (TM) rarely was reported. The exact mechanism for the development of CB-28PT is not well known. Aim To find out causes of CB-28PT cytopenia. Method We retrospectively analyzed data (HLA mismatch status, HLA antibody status of patients, KIR gene mismatch status, KIR-ligand matching status, donor/patient CMV status, donor/patient age and sex) of 93 TM patients underwent HLA 8/8 fully matched or 7/8 matched unrelated donor HSCT. All the patients used sole NF-08-TM protocol with median follow-up time of 19 (r: 2-44) months. Results Results show a significant association between DRB1 mismatch and CB-28PT (P = 0.012). In addition, presence of Class I HLA antibody in the patient’s sera seems increase the chance of CB-28PT. Finally, the matching between inhibitory KIR2DL1 and their corresponding ligand HLA-C2 has a protective effect for CB-28PT. Conclusion We propose that CB-28PT may be a primary manifestation of cGVHD in pediatric TM patients undergoing HSCT positive influenced by HLA DRB1 mismatch, HLA class I antibody and negatively affected by KIR-ligand match. Disclosures No relevant conflicts of interest to declare.

Unrelated Cord Blood Following Haploidentical HSCT with Post-Transplant Cyclophosphamide Improves Results of Alternative Donor Transplant in Thalassemia Major

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5531-5531
Author(s):  
Chunfu Li ◽  
Yuelin He ◽  
Jianyun Liao ◽  
Wenfeng Xu ◽  
Fuyu Pei ◽  
...  
Keyword(s):  
Cord Blood ◽  
Thalassemia Major ◽  
Current Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Alternative Donor ◽  
Unrelated Cord Blood ◽  
F 14 ◽  
Donor Transplant

Abstract Background: Hematopoietic stem cell transplantation (HSCT) is cure for thalassemia major (TM). However, a suitable donor (HLA matched sibling and unrelated donor) for HSCT is less than 50%. Alternative donors were recently used in TM HSCT. Some study have found that thalassemia-free survival (TFS) was approximately 70% in haploidentical HSCT (h-HSCT) or unrelated cord blood (UCB) transplant for TM patients. So, it is necessary to find out a better h-HSCT for TM patients. In our early practice in leukemic HSCT we found that outcomes were improved by adding UCB to post-transplant cyclophosphamide (PT/Cy) h-HSCT. The latter associated with high mortality related transplant (32%). Henceforth, we used this termed haplocord transplant in TM. Aim: To develop a high TFS h-HSCT protocol for TM patients. Patients and methods First 10 patients with median age 8 (5-17) old years received NF-13-PT/Cy-TM protocol (fig. 1), in which, UCB was added on day 6 after PT/CY h-HSCT. Following 9 patients with age 9 (4-15) old years received NF-14-PT/Cy-TM protocol (fig. 2), in which three doses Thymoglobuline were added to NF-13-PT/Cy-TM protocol. Cyclophosphamide on day 3 and day 4 after transplant were both GVHD prophylaxis for h-HSCT and conditioning for UCB transplant. The HLA (at HLA-A, -B, -C and ¨CDRB1) for the pair of recipient and donor was 2-loci and more mismatched in h-HSCT and 2-loci and less mismatched in UCB. Results The results of haplocord transplants for all patients were showed in table 1. For first 10 patients, final cord blood engrafted in 4 patients; final haploidentical donor engrafted in 3 patients, 2 patients had a primary rejection. One had a secondary rejection and gave up therapy and died of infection. One patient died of grade IV acute GVHD. TFS is 6/10. For second group patients, final cord blood engrafted in 4 patients; final haploidentical donor engrafted in 3 patients, mixed donor engrafted in 2. No patient rejected his graft; All 9 patients live with transfusion independence. Summary Our data showed that UCB followed PT/Cy h-HSCT using NF-14-PT/Cy-TM protocol improved the results of alternative donor transplant in thalassemia major. Registered in Clinical Trials: NCT02126046, Table 1. Case Gender/Age(Y) TransplantTime Months After Transplantation Last engraftment(Month) Current Status 1 2 3 4 5 6 1 M/8 2012.09 Mix Mix Mix Mix Mix Mix CB (15) Alive 2 M/5 2012.11 CB CB CB CB CB CB CB Alive 3 M/6 2013.01 / / / / / / / Reject 4 M/17 2013.03 PB PB PB PB PB PB PB Alive 5 M/11 2013.11 Mix Mix Mix Mix Mix Mix Mix (14) Dead 6 M/6 2013.12 Mix Mix Mix CB CB CB CB Alive 7 F/17 2014.03 Mix Mix Mix CB CB CB CB Alive 8 F/7 2014.05 PB PB PB PB PB PB PB Alive 9 F/14 2014.05 PB PB PB Dead / / PB (3) Dead 10 M/8 2014.05 / / / / / / / Reject 11 M/9 2014.08 Mix PB PB PB PB PB PB Alive 12 M/9 2014.08 Mix PB PB Mix Mix Mix PB (7) Alive 13 M/9 2014.10 Mix Mix Mix Mix Mix Mix Mix (9) Alive 14 M/4 2014.10 Mix Mix CB CB CB CB CB Alive 15 F/7 2014.11 PB PB PB PB PB PB PB Alive 16 M/8 2014.12 Mix Mix Mix Mix Mix CB CB Alive 17 M/15 2014.12 Mix Mix Mix CB CB CB CB Alive 18 M/14 2015.03 PB PB PB PB PB Alive 19 F/14 2015.06 Mix CB CB Alive PB: Haploidetical PBSC; CB: cord blood Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplantation for Pesaro IIIβ-Thalassemia Major Using Fludarabine-Based Myeloablative or Non-Myeloablative Conditioning Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3822-3822
Author(s):  
Kanger Zhu ◽  
Jian Gu ◽  
Tao Zhang ◽  
Juan Zhong
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem

Abstract Objective : To explore the efficacy of Fludarabine-based myeloablative or non-myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for classIII thalassemia major with regard to regimen toxicity, graft rejection, and disease-free survival (DFS). Methods: From June 2001 to October 2004, 8 patients underwent allo-HSCT in our BMT unit, including 5 male and 3 female, with median age 5 (3 ~ 19) years. Four patients received graft from sibling donor, including cord blood and peripheral blood stem cells, and the remaining 4 patients received graft from unrelated donors, including bone marrow and peripheral blood stem cells. Fludarabine (FDR) was added into the standard BU/CY regimen, consisting of FDR, BU, CY and ATG. Six patients received myeloablative stem cell transplantation and the remaining 2 patients with evidence of organ damage from iron-overload received nonmyeloablative unrelated donor stem cell transplantation. All patients received Cyclosporine A and Methotrexate for GVHD prophylaxis. Results: Eight patients were successfully engrafted with the median time of absolute neutrophil count (ANC) more than 0.5 ×109 /L was day +13 (+9 ~ +14), and the median time of platelet count more than 20 ×109 /L was day +25 (+8 ~ +39). Two patients died of grade IV aGVHD. The regimen-related toxicity (gradeImucositis, gradeII hemorrhagic cystitis, and gradeIhepatic toxicity) occurred in 3 patients. At a median follow up of 24 (8~48) months, the probability of DFS was 75%, including the two patients given nonmyeloablative stem cell transplantation from unrelated donor. Conclusion: Fludarabine-based conditioning regimen for allo-HSCT in Pesaro III thalassemia major was well tolerated, without increasing toxicity, and associated with durable engraftment and higher rate of DFS (75%). The successful transplantation from unrelated donors using nonmyeloablative conditioning showed that thalassemia clone can be eradicated by the reduced intensity HSCT, which relies upon immunosuppressive rather than myeloablative conditioning to facilitate engraftment of donor cells, and is a novel approach for the treatment of the patients with evidence of organ damage from iron-overload.

Comparison of Outcomes for Non-Myeloablative (NMA) and Myeloablative (MA) Conditioning for Adults with Acute Lymphoblastic Leukaemia (ALL) in First and Second Complete Remission (CR): a Center for International Blood and Marrow Transplant Research (CIBMTR) Analyisis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 872-872 ◽  
Author(s):  
David I. Marks ◽  
Tao Wang ◽  
Waleska S. Peréz ◽  
Donald W. Bunjes ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Conditioning Group ◽  
T Cell Depletion ◽  
Hematopoietic Stem ◽  
Donor Transplant

Abstract Abstract 872 The efficacy of reduced intensity or NMA conditioning for allogeneic hematopoietic stem cell transplantation (HCT) for adults with ALL is uncertain. Using CIBMTR data we compared the outcomes of 92 patients ≥16 years who had NMA conditioning with 1421 patients who had myeloablative conditioning (MC) for allografts using sibling and unrelated donors for ALL in CR1 or CR2. Conditioning in the NMA group included regimens containing busulfan ≤ 9 mg/kg (27), melphalan ≤ 150 mg/m2 (23) or low-dose total body irradiation (36) and others (7). The NMA conditioning group were older (median 45 vs. 28 years, p<0.001) and more received peripheral blood grafts (73% vs. 43%, p<0.001). Other major potential prognostic factors were similar in the two groups. After a median follow-up of 54 vs. 38 months respectively, the NMA vs. MA conditioning groups had slightly less acute grade 2-4 graft-vs-host-disease (GVHD), less chronic GVHD but similar transplant-related mortality (TRM). However the NMA conditioning group experienced slightly more relapse (35% vs. 26%, p=0.08) yet similar overall survival (OS) (Figure): Outcome:MANMAP-value Acute GVHD @ 100 days, grades (2-4)46 (43-49)39 (29-49)0.16 Chronic GVHD @ 3 years42 (39-44)34 (24-44)0.16 TRM @ 3 years, %33 (31-36)32 (23-43)0.86 Relapse @ 3 years, %26 (23-38)35 (25-46)0.08 Leukemia-free survival (LFS) @ 3 years, %41 (38-44)32 (22-43)0.12 OS @ 3 years, %43 (40-46)38 (28-49)0.39 Multivariate analysis showed that a low Karnofsky score (KPS) and T cell depletion were associated with higher TRM but conditioning intensity had no impact on TRM (RR with NMA 0.97, P=0.89). Relapse risk with NMA conditioning was slightly, but not significantly higher ( (RR)=1.34, p=0.15) as was a CR2, particularly with a short (<12 months) initial CR (RR=2.74; longer remission (12 months) RR1.51, P<0.0001). Multivariate analysis demonstrated significantly improved OS with: KPS>80, CR1, lower WBC, no extramedullary disease, a well matched unrelated or a sibling donor, transplant since 2001, in younger patients (<30y), conditioning without TBI and GVHD prophylaxis without T-cell depletion. However ATG use did not affect survival.. The most common cause of death was relapse; which was similar in MA and NMA HCT (46% vs. 35%). Despite the older age in the NMA group, OS and LFS at 3 years was similar to those receiving MA HCT. In comparing the outcomes of NMA and MA conditioning in sibling vs. unrelated donor transplant recipients we found that there was slightly, but not significantly more relapse with NMA [34 (18-52)% vs. 26 (23-30)%, p=NS and 36 (24-49)% vs. 25 (22-28)%, p=NS respectively]. This was associated with similar OS of 40 (23-59)% vs. 50 (45-54)% and 37 (25-50) vs. 38 (34-41)% in the sibling and unrelated donor groups. Conclusions: These data suggest that NMA conditioning is worthy of investigation in prospective clinical trials of adult ALL. These trials should include both well matched unrelated and related donors, but importantly, NMA conditioning may not fully overcome the adverse impact of poor pre-HCT KPS on outcome. >Disclosures: No relevant conflicts of interest to declare.

Circulating Endothelial Cells Enumeration Is a Helpful Tool In The Diagnosis Of GvHD In Patients Undergoing Allogeneic Hematopoietic Stem Cells Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2068-2068
Author(s):  
Camillo Almici ◽  
Cristina Skert ◽  
Rosanna Verardi ◽  
Andrea Di Palma ◽  
Andrea Bianchetti ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Multivariate Analysis ◽  
Early Phase ◽  
Healthy Subjects ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Allo-HSCT can be burdened by life-threatening complications, being GvHD the major cause of morbility and mortality. Clinical and physio-pathological evidences showed that vascular endothelium could be a target of GvHD in very early phase; therefore markers of endothelial damage are warranted as valuable support in GvHD diagnosis. We conducted a study with primary endpoint to identify and count circulating endothelial cells (CEC) in peripheral blood of patients undergoing allo-HSCT as a function of endothelial damage. The CellSearch System® is used to capture and enumerate CEC. Enriched and stained cells are dispensed into a MagNest® cartridge that is scanned and individual images of cells are scored as CEC, based on CD146+, CD105+, DAPI+ and CD45- phenotype. Patients undergoing allo-HSCT were tested before (T1), after the conditioning regimen (T2), at engraftment (T3), at GvHD onset (T4) and at 1 weeks after steroids treatment (T5). Ten healthy subjects served as controls. We enrolled 40 patients with hematologic neoplastic diseases (7 HD, 13 AML, 5 ALL, 8 MM, 3 CLL, 1 NHL, 1 CML, 2 SAA) undergoing allo-HSCT from either HLA-matched familial (n=12) or unrelated donor (n=28). GvHD (grade I-IV) manifested in 19/39 patients. No clinical and transplant characteristics differences were present between patients with and without GvHD. The median CEC/ml pre allo-HSCT was 20 (n=40, range 4-718), in comparison to a value of 2 (range 1-14) in the 10 healthy subjects. At time of engraftment CEC/ml were 47 (range 16-148) in patients with GvHD and 92 (range 23-276) in patients without GvHD (P=0.006). This difference remained significant in multivariate analysis by logistic regression model (OR 0.97, 95% C.I. 0.96-0.99; P=0.02). At GvHD onset, the relative increase of CEC counts (T4 vs T3) was 44% (range, -43 - 569%) in GvHD patients versus 0% (range, -49 – 2%) in patients without GvHD (P=0.003), being confirmed in multivariate analysis (OR 1.04, 95% C.I. 1.0-1.08; P=0.04). Circulating endothelial cells can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT. The confirmation of the clinical utility of CEC counts in a larger series of patients, together with the use of a semi-automatic, standardized and reproducible technology, will allow a valuable help in the diagnostic definition of GvHD in early phase, and moreover could be a valid complement in the prognostic stratification of patients candidates to allo-HSCT. Disclosures: No relevant conflicts of interest to declare.

Analysis of Infection-Related Mortality in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Refractory/Relapse Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4513-4513
Author(s):  
Ren Lin ◽  
Jing Sun ◽  
Yujing Mao ◽  
Mengxia Zhao ◽  
Qifa Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Leukemia ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Underlying Diseases ◽  
Donor Transplant ◽  
Related Mortality

Abstract Abstract 4513 Background Infection-related mortality (IRM) is a major cause of transplant-related mortality (TRM) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, the data about IRM in refractory/relapse acute leukemia patients undergoing allo-HSCT was scarce. We conducted a retrospective study to describe the incidence, causes and risk factors for IRM in recipients with refractory/relapse acute leukemia at a single center. Methods Clinic datas of 127 cases received transplant for refractory/relapse acute leukemia between January 1997 and August 2011 were reviewed. There were 67 cases died at the end of follow-up. In this 67 cases, 27 patients were female and 40 were male; the media age was 31 years (range, 11–61).Uderlying disease was acute myeloid leukemia (AML) in 37 cases, acute lymphoblastic leukemia (ALL) in 21 and acute leukemia of ambiguous lineage in 9. Status of underlying diseases was CR in 19 cases, PR in 15 and NR in 33. There were 25 cases with residual infection diseases before HSCT, including 21 in stable state and 4 in active state with effective control. A total of 59 cases received the conditioning regimen which is 4.5Gy TBI for 2 days and CTX 60mg·kg−1·d−1 for 2 days and 8 patients received busulfan 3.2 mg·kg−1·d−1 for 4 days and CTX 60mg·kg−1·d−1 for 2 days. Patients with PR and NR status of underlying diseases also received fludarabine 50mg·d−1 for 5 days and cytarabine 2 g·d−1 for 5 days as the conditioning regimen. Forty-two cases received related-donor transplant and 25 received unrelated-donor transplant; 30 cases had HLA typing (HLA-A, B and DR) matched-family donor, 12 cases has mismatched-family donors and 25 cases had unrelated-donors. The most common source of stem cells for HSCT was the peripheral blood (n=49), followed by bone marrow plus peripheral blood (n=10) and bone marrow (n=8). Cyclosporine A (CsA) with methotrexate (MTX) (on days +1, +3 and +6) was administered for GVHD prophylaxis in patients undergoing HLA-matched sibling donor transplantation. CsA only or CsA with MTX (on days +1 and +3) was administered for GVHD prophylaxis in patients not received CR before transplant. Patients receiving an unrelated donor or HLA-mismatched sibling donor transplant received CsA + MTX and human antithymocyte globulin (ATG 6–7.5 mg/kg) as GVHD prophylaxis. Logistic regression was used for the identification of risk factors of IRM. Results Within a median 23 months follow-up for patients alive, 67 cases died including 36 died of leukemia relapse and 31 died of TRM. The incidence of 5-years overall survival was 35.2% whereas disease-free survival was 30.8%. Of the 127 cases, 36 cases occurred IRM and the 2-year cumulative incidence of IRM was 36.6%. Fungal infections were responsible for a major proportion of the cases of IRM followed by virus and bacteria infections. Multivariate analyses showed II∼IV°aGVHD (OR=3.017, 95%CI 1.007–9.041, P=0.049) and IFI (OR=3.223, 95%CI 1.103–9.421, P=0.032) were the risk factors of IRM. Conclusions As a common cause of transplant-related mortality, IRM occurred more frequently in refractory/relapse acute leukemia than in the standard-risk patients. Reduction of IRM will require effective prophylaxis and treatment of severe GVHD. Disclosures: No relevant conflicts of interest to declare.

HLA-Haploidentical TCR αβ/CD19-Depleted Hematopoietic Stem Cell Transplantation in Children with Fanconi Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2287-2287
Author(s):  
Luisa Strocchio ◽  
Pietro Merli ◽  
Alice Bertaina ◽  
Luciana Vinti ◽  
Letizia Pomponia Brescia ◽  
...  
Keyword(s):  
B Cells ◽  
Fanconi Anemia ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Introduction. Allogeneic HSCT currently represents the only consolidated curative approach for Fanconi anemia (FA) patients, with best results observed in the HLA-identical sibling setting. For patients lacking an HLA-matched related or unrelated donor, haploidentical HSCT virtually assures the opportunity for nearly all patients to benefit from HSCT, offering the advantage of immediate accessibility to the transplant procedure. In order to overcome the limitation of delayed immune recovery, historically associated with this type of allograft, in the last few years we developed a novel method of ex vivo graft manipulation, consisting of the negative depletion of T-cell receptor (TCR) αβ+ T-lymphocytes and CD19 B-cells from peripheral blood stem cells (PBSC) grafts (ClinicalTrial.gov identifier: NCT01810120) (Bertaina el al., Blood 2014). Here we report our analysis in a subgroup of FA patients given TCRαβ/CD19-depleted haploidentical HSCT at our Institution. Patients and methods. Ten consecutive FA patients (6 girls and 4 boys) underwent a TCRαβ/CD19-depleted HSCT from an HLA-haploidentical relative between September 2011 and July 2015. Median age at diagnosis was 6.6 (range 2.7-22.0) years and median age at time of transplantation was 8.1 (range 4.4-22.2) years. The conditioning regimen included Cyclophosphamide 300 mg/m2/day and Fludarabine 30 mg/m2/day for 4 consecutive days (days -6 to -3), with 200 cGy single-dose TBI. Pretransplantation Fresenius® ATG was administered at a dose of 4 mg/kg/day for 3 consecutive days (days -5 to -3) in order to prevent both graft failure and graft-versus-host disease (GVHD). All patients received Rituximab 200 mg/m2 to reduce the risk of Epstein-Barr virus-related post-transplant lymphoproliferative disorders. Selective removal of TCRαβ+ and B-cells was performed on G-CSF-mobilized donor PBSC through labeling with biotinylated anti-TCRαβ antibodies and anti-CD19 antibodies, followed by incubation with anti-biotin antibodies conjugated to paramagnetic beads (CliniMACS; Miltenyi Biotec, Bergisch Gladbach, Germany). No immunosuppressive therapy was administered as post-transplantation prophylaxis against GVHD. Results. The TCRαβ/CD19-depletedgrafts contained a median of 20.40 x106/kg (range 15.80-33.40) CD34+ cells, 5.60 x106/kg (range 1.78-69.60) CD3+ lymphocytes, 0.021 x106/kg (range 0.002-0.043) TCRαβ+ lymphocytes, 5.60 x106/kg (range 1.78-69.60) TCRγδ+ lymphocytes, 0.036 x106/kg (range 0.013-0.079) CD20+ lymphocytes, and 45.30 x106/kg (range 16.2-177.0) NK cells. Engraftment with sustained full donor chimerism was achieved in 9 out of 10 patients, the cumulative incidence of graft rejection being 10% (95% CI, 0-26.8). The patient who rejected his first allograft achieved a complete engraftment after a second HSCT from one-antigen mismatched unrelated donor. No secondary graft failures were observed. The median time for neutrophil and platelet engraftment was 12 days (range, 9-15) and 9 days (range, 8-12), respectively. No patient experienced acute or chronic GVHD in the follow-up period. No transplant-related deaths occurred in our cohort. With a median follow-up of 28 months (range 13.2-39.1), the Kaplan-Meier estimates of OS and DFS were both 100%, while the EFS probability was 90% (95% CI, 47.3-98.5). Discussion. These data suggest that haploidentical HSCT after removal of TCRαβ+ and CD19+ lymphocytes is able to guarantee engraftment with excellent OS and DFS in patients affected by FA. Moreover, given the very low incidence of both acute and chronic GVHD, which has been shown to contribute to the increased risk of developing late post-transplantation malignancies in FA patients, this approach can be considered a very attractive option for FA patients in need of an allograft and lacking an HLA-identical family donor. 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.

scholarly journals Outcome of Severe Aplastic Anemia Post Allogenic Stem Cell Transplant with Mycophenolate and Calcineurin Inhibitor for Graft Versus Host Disease Prophylaxis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4879-4879
Author(s):  
Omar Albanyan ◽  
Hyejeong Jang ◽  
Seongho Kim ◽  
Andrew Kin ◽  
Asif Alavi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Matched Donor

Abstract Introduction: Severe aplastic anemia (SAA) is a rare hematopoietic stem cell disorder characterized by hypocellular marrow and pancytopenia. Multiple factors play an important role in treatment approach include age, comorbidities, degree of pancytopenia and availability of stem cell donor to either immunosuppression irrespective (IST) or allogenic hematopoietic stem cell transplant (alloSCT). The use of nonmyeloablative conditioning regimen has improved the outcomes, however the choice for post-transplant GVHD prophylaxis remain a topic of debate. The use of mycophenolate mofetil (MMF) has been used as an alternative for methotrexate (MTX) as has shown to be associated with lower incidence of mucositis and shorter time to engraftment. Methods: We retrospectively evaluated consecutive adult patients with SAA who underwent alloSCT at Karmanoc Cancer Institute. All patients received fludarabine, cyclophosphamide and antithymocyte globulin for conditioning regimen with calcineurin inhibitors (CNI) and MMF for GVHD prophylaxis. MMF was started at day -3 at 15 mg/kg three times daily and stopped at day +30 in the absence of active GVHD. The primary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and overall survival (OS). Secondary objectives were to evaluate time to engraftment, days of hospitalization and incidence of mucositis. Results: From January 2005 and May 2019, 33 patients with SAA underwent alloSCT. Patient characteristics are detailed in Table 1. Median age was 36 years (range, 18-71). Twenty-seven patients received bone marrow stem cells (82%) and six patients received peripheral blood stem cells (18%). Thirty patients (91%) received 8/8 HLA matched donor and three patients (9%) received 7/8 HLA matched donor. Sixteen patients (48%) received stem cells from sibling donor and 17 patients (52%) received stem cells from unrelated donor. Thirteen patients (39%) had received IST prior to alloSCT, and 20 patients (61%) received upfront alloSCT. For GVHD prophylaxis all patients received MMF and CNI (tacrolimus=32, and cyclosporine=1). Median time from diagnosis to transplant was 15.8 months for patients who received IST prior to alloSCT and 2 months for patients who received upfront alloSCT. Median time to platelet engraftment was 13.5 days and neutrophil engraftment was 12 days, while one patient experienced graft failure. The median number of days for hospital stay were 25 days. Four patients (11%) developed grade I-II mucositis, no grade III-IV mucositis was observed in the first 30 days and 6 patients had CMV reactivation. The 100-day cumulative incidence rate of grade II-IV aGVHD was 21.2% (95% CI, 9.2 - 36.5), grade III-IV aGVHD was 9.1% (2.3-21.9) and 1-year CIR of cGVHD was 21.2% (95% CI, 9.2-36.5). Comparing patients who received IST prior to alloSCT versus upfront alloSCT, the 100-day CIR of grade II-IV aGVHD was 30.8% (95% CI, 8.2 - 56.5) and 15% (95% CI, 3.6 - 34.0), respectively, (Gray p=0.26) and the 3-year CIR of cGVHD was 39.6% (95% CI, 13.1 - 65.5) and 27.8% (95% CI, 9.2 - 50.3), respectively, (Gray p=0.37). Comparing patients who received alloSCT from related versus unrelated donor, 100-day CIR of II-IV aGVHD was 12.5% (95% CI, 1.9 - 33.6) and 29.4% (95% CI, 10.2 - 51.9), respectively, (Gray p=0.26), and the 3-year CIR of cGVHD was 34.2% (95% CI, 11.4 - 58.9) and 29.4% (95% CI, 10.1 - 52.0), respectively (Gray p=0.90). Median follow up of surviving patient was 5 years (95% CI, 3.1-6.8). Three-year OS was 87% (95% CI, 75.7- 99.9) and median OS was not reached. Six patients died by the time of the analysis, one patient died from graft failure (86 days after transplant from 8/8 HLA MUD), two patients died due infectious complications (808 days and 1637 days after transplant), three patients died due to multiorgan failure (215, 297 and 1097 days after transplant). Conclusion: Our data with use of CNI and MMF for GVHD prophylaxis for SAA following alloSCT with nonmyeloablative conditioning regimen showed that the rate of mucositis was low, engraftment time was rapid, and hospitalization was short, while OS, rates of acute and chronic GVDH were comparable to previously published rates with CNI and MTX-based GVHD prophylaxis. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

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