Successful allogeneic engraftment of mismatched unrelated cord blood following a nonmyeloablative preparative regimen

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3486-3488 ◽  
Author(s):  
David A. Rizzieri ◽  
Gwynn D. Long ◽  
James J. Vredenburgh ◽  
Christina Gasparetto ◽  
Ashley Morris ◽  
...  
Keyword(s):  
Cord Blood ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Preparative Regimen ◽  
Unrelated Donors ◽  
Alternative Donor ◽  
Matched Sibling ◽  
Cord Blood Cells ◽  
Unrelated Cord Blood

Abstract Reduction in the toxicity of allogeneic transplantation with nonmyeloablative induction regimens has expanded the scope of practice to older and more debilitated patients. However, the limited availability of matched sibling donors requires that alternative donor sources be investigated. Reported here are 2 cases of patients with advanced hematologic malignancies without matched siblings, partially matched family members, or matched unrelated donors who successfully underwent nonmyeloablative conditioning therapy followed by infusion of partially matched, unrelated-donor cord blood cells. The patients are in remission and remain 100% donor as assessed by short tandem repeat analysis of the marrow 6 and 12 months following transplantation.

Results of Alternative Donor Search in Adult Patients with Severe Sickle Cell Disease (SCD) Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2260-2260 ◽  
Author(s):  
Matthew M. Hsieh ◽  
Jennifer Wilder ◽  
Courtney Fitzhugh ◽  
Beth Link ◽  
John F. Tisdale
Keyword(s):  
Cord Blood ◽  
Great Majority ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Potential Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Sibling Donor ◽  
Alternative Donor ◽  
Matched Sibling

Abstract Supportive care has improved the outlook for patients with SCD, but life expectancy remains considerably shorter than those without SCD. The major causes of mortality are end-organ failure, stroke, pulmonary disease, and acute vaso-occlusive crises (VOC). Myeloablative allogeneic HSCT in children under age 16 is curative in the majority. However organ damage that meets severity criteria for HSCT may not become evident until adulthood, at which time conventional myeloablative transplant is no longer an option. Additionally, the great majority of SCD patients do not have a 6/6 HLA-matched sibling donor available. Reduced-intensity conditioning may extend this potentially curative treatment to adults with SCD. Since non-myeloablative transplants may result in mixed donor chimerism, major ABO-mismatch may lead to red cell aplasia, and therefore should be avoided. Finally, cell dose is likely an important parameter in non-myeloablative transplant regimens, potentially further limiting donor availability. We initiated an IRB approved non-myeloablative allogeneic HSCT program for adults with severe SCD for whom a matched sibling donor is available. For those without related donors, we devised a search strategy for alternative donors to establish the feasibility of matched unrelated donor (MUD) or umbilical cord blood (UCB) HSCT. HLA typing was performed for potential donors and patients who on initial screen met at least one the following criteria: stroke, pulmonary hypertension, sickle related nephropathy, or frequent VOC/ACS not improved by HU. Typing at the serologic level was performed for HLA-A,-B, and at the allele level for HLA-DR B1. For patients without matched sibling donors, searches in the National Marrow Donor Program for marrow and cord blood donors were initiated. Since 2003, we performed initial screening in >100 patients, typed 58 potential recipients and 85 donors, and identified 13 potential recipients (age ≥ 16 years) with matched sibling donors. Two were excluded because of major ABO incompatibility. Among the remaining 43, 10 patients who met all study criteria on full screening were selected for alternative donor searching. MUD search results identified a median of 2.5 (range 0–18) 6/6 HLA-matched donor available. Five individuals had 0, four had 4–6, and one had >15 potential donors. UCB search revealed no patient had a 6/6 HLA-matched, two had 15–16 5/6 HLA-matched, and five had 11–190 4/6 potential donor UCB units. The median UCB units containing ≥ 2 × 10e7 nucleated cells per kg were 0 for 6/6 HLA-matched (range 0–1), 0 for 5/6 HLA-matched (range 0–19), and 8.5 for 4/6 HLA-matched (range 0–190). When ethnic haplotype and allelic frequency, the available ABO status, the likelihood of requiring two UCB units for each adult recipient were considered, 5 had neither MUD nor UCB units available, 2 only had potential UCB units available, and 3 had both MUD and UCB units available. The majority of adults with severe SCD who are eligible for non-ablative allo-HSCT do not have matched sibling donors. Our search shows that the minority of African-American adults have potential alternative donors, 10% and 50% MUD and UCB, respectively. These numbers will likely be reduced when major ABO mismatches are excluded. Further, unlike pediatric patients, one cord blood unit may not provide sufficient cells to overcome the barrier of graft rejection in most adults. Given these limitations, the feasibility of haplo-identical family donor allo-HSCT should be investigated.

A Prospective Study on the Feasibility of Related and Unrelated Donor Search and Hematopoietic Cell Transplantation for Adults with Acute Leukemia at 31 European Transplant Centers

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2385-2385
Author(s):  
Vanderson Rocha ◽  
Mutlu Arat ◽  
Vladimir Koza ◽  
Norbet C Gorin ◽  
Augustin Ferrant ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Hla Typing ◽  
First Year ◽  
Unrelated Donor ◽  
Alternative Donor ◽  
Family Donor ◽  
Unrelated Cord Blood ◽  
One Year

Abstract Currently, a donor can be virtually found for all patients with an indication for allo-transplantation due to the increased number of hematopoietic stem cell (HSC) donors and increasing use of umbilical cord blood and haplo-transplants. In this study, we have addressed the question of the feasibility of searching HSC donors grafts [HLA-matched sibling donor (MSD), and alternative donors] and performing such transplants or other treatments (such as autologous HSC transplant or chemotherapy) for adults with acute leukemia for whom an indication of allo-HSCT could be planned during the course of their disease. The second objective was to compare in an “intent to treat” analysis, LFS according to planned strategy treatment. Patients were included at HLA typing test. A specific questionnaire was completed specifying the initial strategies planned for each patient and their changes over the period: at HLA typing, after 3, 6, 9, 12 months after the registration, and twice a year for the following 2 years. From 2003 to 2006, 702 adults were enrolled by 31 EBMT centres, 490 had AML, 212 ALL. HLA typing was performed for 443 patients at diagnosis, 172 after first CR, 11 after CR2, and 64 in more advanced phase. Median follow-up was 31 months, median age was 42-years (18–75); 207 patients were aged more than 50 years. A MSD was found for 309 patients (44%). Of 309 patients, 290 patients had 1 MSD, 17 patients 2 MSD and only 2 patients more than 2 donors. In 40 cases where the MDS was found the transplant centres did not planned to perform the transplant. A transplant using a haploidentical donor was planned in 4 cases. At the end, 273 patients were planned to be transplanted from a family donor (269 from a MSD and 4 from an haplo). For the remaining 429 patients, the indication of an auto-HCT was made in 85 (20%) patients, use of chemotherapy as post-remission therapy in 142 (33%) and indication of an allo-HSCT with an alternative donor in 202 (47%). Of those 202 patients, the transplant centres were keen to search for a cord blood donor in 72 cases and for a haplo donor in 11 cases. Analysing the treatment received at the last follow-up and comparing with the strategy planned at the registration, 215 of 270 (80%) patients were transplanted with a family donor, 112 of 142 (79%) patients were still receiving chemotherapy, 53 of 85 (62%) received an autograft and 118 of 202 (58%) received an unrelated transplant. At last follow-up, 448 patients of 702 patients included received an HSCT (64%). Probability of survival at 2 years for 702 patients was 55%. Interval from HLA typing and HSCT was 125 days for MSD, 148 days for unrelated donor, 167 days for unrelated cord blood and 149 days for autologous transplantation. Cumulative incidence function at one year (CIF; using death as a competing event) for receiving an allograft was 81% if the strategy planned was an allograft with a MSD, 57% for those patients for whom an alternative donor was searched and 6% for those patients for whom an allo-transplant was not planed at inclusion. However, CIF at 1-year for really receiving an allograft was 74% in case of MSD, and only 30% for those patients not having an HLA identical siblingAt 2-years, LFS by initial planned strategy at HLA typing was 43% for those patients in whom a donor search was planned, 47% for those with a planned autologous HSCT, 46% for those with planned chemotherapy and 49% for those with a family transplant. In conclusion, the majority of patients (80%) with AL in European centres are HLA typed at diagnosis or CR1. The majority of patients received a MSD as planned treatment in the first year after HLA typing, in the absence of MSD an alternative donor was searched only for 51% of patients and CIF at one year for performing an allotransplant was 30% however in case of searching for alternative donor, transplantation could be performed in 57% of the cases in the first year. Surprisingly, searching for other alternative donors such as unrelated cord blood or haplo-identical donors, was only done for a small proportion of patients, in spite of encouraging results with both strategies. Therefore, in retrospective studies comparing outcomes of HLA identical sibling, and other alternative donor transplants there is a potential bias linked to the decision to search or not in half of the cases, that is probably linked to patients-, disease- and centre-related factors.

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.

scholarly journals Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Li ◽  
Xiaofan Li ◽  
Yiling Chen ◽  
Duihong Li ◽  
Xianling Chen ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Post Transplantation ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Unrelated Cord Blood

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 vs. 56.5%), p>0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175–0.691; p=0.0025), DFS (HR 0.402, 95% CI, 0.208–0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120–0.457, p<0.0001) compared to the single cord group. The 2-year’s probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p>0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.

Alternative Donor Transplantation For Adults With Lymphoma: Comparison Of Umbilical Cord Blood Versus 8/8 HLA-Matched Donor (URD) Versus 7/8 URD

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 161-161
Author(s):  
Veronika Bachanova ◽  
Claudio Brunstein ◽  
Linda J. Burns ◽  
Tao Wang ◽  
Jeanette Carreras ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Significant Difference ◽  
Alternative Donor ◽  
Matched Sibling

Abstract Allogeneic donor hematopoietic cell transplantation (HCT) is increasingly used to treat relapsed lymphoma with curative intent; however, many patients will not have a suitable matched sibling donor. Transplant centers are investigating the use of alternative stem cell sources although data comparing outcomes by stem cell source are limited. We compared outcomes of 1593 non-Hodgkin and Hodgkin lymphoma patients who underwent alternative donor HCT from 2000-2010 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Umbilical cord blood (UCB) (n=142), 8/8 (human leukocyte antigen [HLA] –A, B, C, and DRB1) matched adult unrelated donor (URD) (n=1176) and 7/8 HLA matched URD (n=275) HCT recipients were followed for a median of 25, 57 and 65 months, respectively. The median age in the 3 groups were UCB: 45 years (range 19-73 yrs), 8/8 URD: 50 (range 18-75 yrs) and 7/8 URD: 45 years (range 18-71yrs). Male gender and mantle cell lymphoma were more frequent in 8/8 URD recipients. 7/8 URD HCT recipients had lower Karnofsky performance scores, and UCB recipients were more likely to be non-Caucasian, have chemosensitive disease and to have undergone HCT in recent years. UCB recipients had inferior neutrophil and platelet engraftment rates at 100 days; however they were less likely to develop acute and chronic graft versus host disease (GVHD) compared to 7/8 URD and 8/8 URD (Table). The cumulative incidence of treatment related mortality (TRM) at 3 years was higher in 7/8 URD. There were no differences among the 3 groups in the 3-year relapse/progression, progression free survival (PFS) or overall survival (OS).Table.OutcomesUCBURD 8/8URD 7/8% (95%CI)% (95%CI)%( (95%CI)P-valueTime to ANC>0.5 x 109/L at 28 days66 (57-73)94 (92-95)94 (90-96)<0.001Platelet recovery ≥ 20 x 109/L at 100 days68 (59-76)86 (84-88)85 (80-89)<0.001Acute GVHD (II-IV) at 100 days26 (19-34)37 (35-40)49 (43-55)<0.0013 years Chronic GVHD at 3 years22 (15-30)51 (48-54)48 (42-54)<0.0013 years Treatment related mortality38 (29-46)35 (32-37)46 (41-52)0.0023 years Relapse/Progression29 (22-37)32 (29-34)25 (20-31)0.1073 years Progression free survival33 (25-42)33 (31-37)29 (23-34)0.1863 years Overall survival44 (35-53)43 (40-46)34 (29-40)0.017 In multivariate analysis stratified for performance status, lymphoma histology, GVHD prophylaxis, and disease status, no significant difference in OS was detected between UCB and 8/8 URD (HR 0.87 [95% CI 0.68-1.12]; p=0.29), UCB and 7/8 URD (HR 1.04 [95% CI 0.78-1.40]; p=0.77), and 8/8 and 7/8 URD (HR 1.19 [95%CI 0.97-1.45; p=0.08). Lower risk of treatment failure (death or relapse; inverse of PFS) was observed in transplants performed after 2007 (HR 0.79 [95% CI 0.66-0.96]; p=0.01) as compared to the time periods 2000-2003. Patients' age, time from diagnosis to HCT, race, history of prior HCT, and conditioning intensity did not influence OS or PFS. In conclusion, our results suggest that UCB and 7/8 URD grafts for patients with advanced lymphoma provide similar survival to 8/8 URD, extending allogeneic HCT to most patients with no suitable matched sibling donors. Graft source needs to be determined by availability, the clinical urgency of transplant, and transplant center experience. Disclosures: No relevant conflicts of interest to declare.

Unrelated Cord Blood Transplants in Children with Acute Leukemia: Experience of a Single Center

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4424-4424
Author(s):  
Rosa Branca Ferreira ◽  
Carlos Pinho Vaz ◽  
Isabel Barbosa ◽  
Susana Roncon ◽  
Fernando Campilho ◽  
...  
Keyword(s):  
Cord Blood ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Gvhd Prophylaxis ◽  
Successful Transplantation ◽  
Unrelated Donors ◽  
Alternative Sources ◽  
Unrelated Cord Blood

Abstract Allogeneic stem cell transplantation is an accepted treatment modality for selected malignant diseases. However, the ability to identify suitable related or unrelated donors can be difficult in some patients (pts). Alternative sources of stem cells such as cord blood (UCB) provide a readily available graft mainly for pediatric patients. Between October 1996 and May 2008, 23 consecutive patients (pts), with a median age of 6 years old (range:1 – 11), 13 male and 10 female, underwent UCB transplant for the treatment of acute lymphoblastic leukemia (n= 15), acute myeloid leukemia (n=7) and acute byphenotypic leukemia (n= 1). Conditioning regimen consisted of intravenous busulfan (3.2 mg/kg/day x 4 days), cyclophosphamide (120 mg/Kg) and rabbit antithymocyte globuline (15 mg/Kg) ±melphalan (140 mg/m2) and GVHD prophylaxis consisted of a calcineurin inhibitor and MMF or MTX. All grafts were HLA mismatched. The median infused cell doses were, respectively 3.2× 107/kg (range: 1.2–21) and 1.27×105/kg (range:0.2–4.3) for nucleated cells (NC) and CD34 + cells. Engraftment occurred in 18 pts (75%). Five pts failed engraftment, of wich 4 underwent a second transplant (3 autologous and 1 haploidentical) and 1 died of infection at day +59. Grade II–IV acute GVHD occurred in 12 pt and chronic GVHD in 2 of 14 pt at risk. With a median follow up of 1,5 years (range: 3 months-9.5 years), overall survival (OS) at 3 years is 40% (± 13%) and event free survival (EFS) at 3 years is 32% (± 11%). Non relapse mortality (NRM) was 13.6 % (± 7.3%). UCB transplants represents a valuable alternative to bone marrow or peripheral blood especially for pts requiring urgent transplant or lacking an HLA matched unrelated donor and having the potential advantage of an immune tolerance allowing successful transplantation despite HLA disparity

Trends In Incidence, Presentation, and Outcomes Of Chronic Graft-Versus-Host Disease In Allogeneic Transplantation- Report From The Center For International Blood and Marrow Transplant Research

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3309-3309
Author(s):  
Sally Arai ◽  
Mukta Arora ◽  
Tao Wang ◽  
Wensheng He ◽  
Daniel R. Couriel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Allogeneic Transplantation ◽  
Recent Time ◽  
Unrelated Donor ◽  
Graft Versus Host ◽  
Time Period ◽  
Matched Sibling ◽  
Time Periods ◽  
Over Time

Abstract There have been considerable changes in the practice of allogeneic transplantation over the last several years. In this study, we evaluate the impact of these changes on chronic graft-versus-host disease (cGVHD), the most important long-term complication. Our study utilized the central database of the CIBMTR to describe time trends for cGVHD incidence, presentation, nonrelapse mortality and overall survival from 1995-2007. The 12-year period was divided into three time periods- 1995-1999, 2000-2003, 2004-2007 to allow for the systematic analysis and description of trends. The trends of cGVHD severity (mild, moderate, severe), type of onset (progressive, interrupted, de novo), and major organ involved over the past years were analyzed using chi-square tests. Cumulative incidence was used to estimate cGVHD incidence and nonrelapse mortality. Death/ 2nd transplant/donor cell infusion/relapse were treated as competing risks for estimation of cumulative incidence of cGVHD. A test of trend was used to estimate HR across time periods. Multivariate logistic regression analysis was used to determine clinical variables affecting the incidence of cGVHD, including the time period of transplant. The study included 26,563 patients with acute leukemia (AML= 10,737, ALL= 6756), chronic myeloid leukemia (n=6341) and myelodysplastic syndrome (n=2729). In the univariate analysis, the incidence of cGVHD was significantly increased in the recent time periods (HR= 1.14, p for test of trend <0.0001). This trend persisted when the incidence was evaluated by donor type (HLA identical sibling-HR=1.17; unrelated donor-HR=1.07; cord blood-HR=1.24, all p < 0.01), graft type (PBSC-HR=1.19; cord blood-HR=1.24, p < 0.01), or conditioning intensity (myeloablative-HR=1.13; reduced intensity-HR=1.16, p< 0.01). In mismatched-related donors (HR=1.08, p=0.24) and bone marrow grafts (HR=1.01,p=0.54) there was no significant change in the incidence of cGVHD. Progressive cGVHD was found to be less frequently diagnosed over time, possibly from the recognition of the late acute classification introduced in 2005. Extensive, moderate and severe categories of cGVHD were more frequent in the two most recent time periods (2000-2003 and 2004-2007), as compared to the earliest time period (1995-1999). Skin was more frequently involved in the recent time period (2004-2007), with greater association of skin involvement at maximum severity reported in peripheral blood (33%), compared with bone marrow (25%), thus graft type appears to have impacted cGVHD presentation. In multivariate analysis, the recent time period (2004-2007) was associated with higher risk of cGVHD when compared to the two earlier time periods (2004-2007 versus 1995-1999, OR 1.19, p<0.0001; 2004-2007 versus 2000-2003, OR 1.13, p=0.002). Use of bone marrow with an unrelated donor (matched or mismatched), and peripheral blood graft with all categories of donor group were associated with higher risk of cGVHD, as compared to the use of bone marrow with a matched sibling donor. The risk of cGVHD was similar between marrow with a matched sibling donor and cord blood (matched or mismatched). In conclusion, this analysis of cGVHD trends over time demonstrates an increased cGVHD incidence in recent years despite controlling for factors in the donor, the graft and the conditioning that are associated with that trend, and serves as a useful reference for future research in the management of cGVHD. Disclosures: No relevant conflicts of interest to declare.

Alternative Donor Transplantation for Aplastic Anemia

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Mary Eapen ◽  
Mary M. Horowitz
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Graft Failure ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Term Survival ◽  
Alternative Donor

AbstractPatients with severe aplastic anemia who do not have a human leukocyte antigen (HLA)-identical sibling generally receive immunosuppressive therapy as a first-line therapy, with allogeneic transplantation being reserved for those who do not have an adequate sustained response. Barriers to the use of unrelated-donor transplantation for aplastic anemia include identifying a suitable alternative donor, and risks of graft failure, regimen-related toxicity, and graft-versus-host disease (GVHD). Despite the more than 14 million adults registered with donor registries worldwide, only approximately 50% of patients of Caucasian descent will have an available and fully HLA-matched unrelated adult donor; the rate is substantially lower for non-Caucasians. While umbilical cord blood allows transplantation with greater donor-recipient HLA disparity (without excessive risk of GVHD), risks of graft failure and transplant-related mortality are higher than after transplantation of adult donor grafts. Among patients with a suitable donor, recent changes in pre-transplant conditioning regimens have lowered the risks of organ toxicity and graft failure. Although advances in donor HLA typing and selection practices and improved GVHD prophylaxis have lowered the risk, GVHD remains an important obstacle to long-term symptom-free survival. Despite these limitations, unrelated-donor transplantation offers the best chance of long-term survival for many patients in whom current immunosuppression strategies are not effective. Wider applicability of alternative-donor transplantation for aplastic anemia will require better approaches to prevent graft failure and GVHD and to expand the pool of unrelated-donor grafts. This includes exploring strategies to effectively use alternative grafts such as umbilical cord blood.

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