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.

Unrelated Cord Blood Transplantation in India: Breaking the Cost Barrier

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4768-4768
Author(s):  
Satya Prakash Yadav ◽  
Anupam Sachdeva
Keyword(s):  
Cord Blood ◽  
Thalassemia Major ◽  
Unrelated Donor ◽  
Class Iii ◽  
Hematopoietic Stem ◽  
Total Cost ◽  
Duration Of Stay ◽  
Unrelated Cord Blood ◽  
The Cost ◽  
Mean Cost

Abstract Abstract 4768 Background – India, with more than a billion population, has a huge burden of blood and cancer disorders many of which can be cured only by hematopoietic stem cell transplantation (HSCT). More than 1500 transplants have been done till 2005 over a 20 year period in about 10 centers out of which 880 have been allogeneic HSCT and all have been from matched related donors (MRD).Unrelated HSCT is the only option for the patients without a MRD. It is almost impossible to find an unrelated matched donor in India due to ethnic diversity and lack of unrelated donor registries. Some public cord blood banks have been set up in India. So finding a suitable cord blood unit within India is possible. Unrelated Cord Blood Transplant (UCBT) is the only feasible option for patients who need to undergo unrelated HSCT in India but lack of experience and huge costs are perceived barriers. Data from USA showed mean cost of graft for pediatric UCBT was $58,910 and mean cost per day survived in first 100 days (excluding graft cost) was $4522 ((Majhail NS et al. Pediatr Blood Cancer 2010;54:138–143). The costs of UCBT among children in India have not been described previously. Method - We calculated the costs of UCBT within the first 100-days among four children who received UCBT at Sir Ganga Ram hospital from April 2008 to Dec 2010. We also analyzed costs of transplantation in relation to patient age, weight, single vs. double cord, conditioning, Graft vs. Host Disease (GVHD) and mean duration of stay before day 100. Results - The 100-day probability of overall survival was 100%. The mean cost per day survived (excluding costs of graft acquisition) was $402 (range $360-460)) for UCBT recipients. Average total cost of each UCBT was $43500 (Range $32000-52000). Average duration of stay in hospital in first 100 days was 89 days (range 75–100). All grafts were procured from a public cord bank in India. Average cost of graft per cord unit was $5000. Diagnosis was thalassemia major-2, Familial Hemophagocytic Lympho Histiocytosis (HLH)-1 and AML-1. Lowest cost was for AML ($32000) and highest was for Pesaro class III thalassemia major ($52000). Mean age was 2.75 years (range 1–5 year). Mean weight was 12.25 kg (range 10–16 kg). Mean cell dose infused was 7 × 107 nucleated cells/kg weight of recipient (range 3–10 × 107nucleated cells/kg). Conditioning was Busulfan and Cyclophosphamide (BuCY) and Rabbit Anti-Thymoglobulin (ATG) for two patients (1 Thalassemia, 1 AML) costing $1500 per patient, Fludarabine & Melphalan and Campath for HLH costing $2500 and Treosulfan, Thiotepa, Fludarabine and ATG for class III thalassemia costing $7500. Mean cost per day for single cord was $385 and for double cord UCBT was $420. One patient rejected the graft. Three engrafted at median of 32 days (range 28 –39 days). GVHD was seen in two patients (both with double cord). CMV reactivation was seen in all cases. Invasive aspergillosis was seen in one patient who had thalassemia and it lead to highest expenditure. Campath based conditioning was associated with maximum hospital stay in child with HLH. All had Lansky score >90 pre-transplant No one needed dialysis, mechanical ventilation or hepatic veno-occlusive disease. Conclusions - Total cost of UCBT in India is less than the cost of the UCBT graft in USA and mean cost per day in India is almost one tenth of cost per day in USA. Low cost of UCBT in India would make this treatment feasible for many more patients who need to undergo unrelated HSCT. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Umbilical Cord Blood (UCB) Transplantation: An Alternative to the Use of Unrelated Volunteer Donors?

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Juliet N. Barker
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Pediatric Patients ◽  
Current Status ◽  
Unrelated Donor ◽  
Donor Pool ◽  
Hematopoietic Stem ◽  
Volunteer Donor ◽  
Potential Alternative

AbstractCryopreserved umbilical cord blood (UCB) from 4-6/6 HLA-A,B antigen and DRB1 allele matched unrelated neonatal donors contains sufficient numbers of hematopoietic stem cells (HSC) to engraft most younger pediatric patients with leukemia. Recent data demonstrate promising results in larger children and adults, as well as in patients with nonmalignant disorders. As a result, the number of UCB transplantations (UCBT) being performed is increasing dramatically. UCB has the clear benefits of rapid availability and a reduced stringency of requirement for HLA match. The latter attribute has the potential to extend the donor pool, which is of great importance for racial and ethnic minorities. Furthermore, new preparative regimens combined with double-unit grafts have been associated with improved engraftment and survival in larger children and adults, making UCBT a viable potential alternative to unrelated volunteer donor transplantation, especially in preference to transplantation using mismatched volunteers. This review summarizes the current status of unrelated donor UCBT and describes both the challenges and current areas of research associated with this HSC source.

scholarly journals Unrelated Cord Blood Transplantation and Post-Transplant Cyclophosphamide (PT-CY)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3332-3332
Author(s):  
Patrizia Chiusolo ◽  
Andrea Bacigalupo ◽  
Simona Sica ◽  
Sabrina Giammarco ◽  
Elisabetta Metafuni ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
High Dose ◽  
Unrelated Donor ◽  
Immune Recovery ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Unrelated Cord Blood

Background .There has been a decrease in the use of unrelated cord blood transplants (UCBT) in the past years: this is probably due to slow hematologic and immune recovery, resulting in a relatively high non relapse mortality (NRM). The addition of anti-thymocyte globulin (ATG) in the conditioning prevents graft versus host disease (GvHD) but makes immune recovery very slow. In addition there is a growing competition of unmanipulated haploidentical transplants. Aim of the study. We have opened a pilot study to test whether high dose post-transplant cyclophosphamide (PT-CY) would prevent GvHD but still allow for robust immune and hematologic recovery . Methods. We have grafted 10 patients with an unrelated CB unit and PT-CY. The conditioning regimen was thiotepa (10 mg/kg), busulfan 9.6 mg/kg and fludarabine 150 mg/m^2 (TBF). GvHD prophylaxis was cyclosporin (CSA) starting day 0 (3 mg/kg/day(i.v.), mycophenolate (MMF) 30 mg/kg starting day +1 (p.o) , and PT-CY 30 mg/kg days +3 and +5. The median patients' age was 58 (43-66), and the median weight was 75 kg (54-85) the diagnosis was AML in 8 patients, Ph'+ALL in one and RAEB in one patient; 6 patients were in remission and 4 had active disease. CB units. The HLA matching of the CB unit was 5/8 antigens/alleles (A,B,C,DRB1) in six patients, 4/8 in two and 2/8 in one. The median nucleated cell dose was 3.1x10^7/kg (range 1.8- 4.5). The ABO was mismatched in all 10 patients. Hematologic recovery: median time to neutrophils 0.5x10^9/l was day 23 days (range 17-27) and the median time to a platelet count of 20x10^9/L was 38 days (range 34-40). The median counts on day +50 were as follows: Hb 9,1 gr/dL (range 8.7-11.1), Neutrophils 2,3 x10e9/L (range 1-5), PLTs 56 x10e9/L (10-90). One patient failed to engraft and received a second transplant from an unrelated donor, which was successful. No patient developed pure red cell aplasia despite 9/10 being ABO major mismatched. CD4 recovery : the median CD4 count on day +50 was 74 /cmm (range 67-116) and on day +100 it was 111/cmm(range 100-136). CMV pre-emptive therapy occurred in 3/6 evaluable patients Outcome: two patients with advanced disease, died early of infections, within day +20. GvHD was seen in 1 patient as a transient rash. No patient was treated for GvHD. No patient developed chronic GvHD. No patient relapsed. Eight patients survive in remission, with a median follow up of 6 months, and a projected one year actuarial survival of 80%. Readmissions were extremely rare. Conclusions. These first 10 patients suggest that UCBT followed by PT-CY, CSA, MMF, as GvHD prophylaxis is feasible and leads to encouraging hematologic and immunologic recovery. We were particularly impressed with the lack of GvHD, the absence of relapses and the good quality of life. Figure Disclosures No relevant conflicts of interest to declare.

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.

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.

Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 351-357 ◽  
Author(s):  
William Reed ◽  
Renée Smith ◽  
Florinna Dekovic ◽  
Joanna Y. Lee ◽  
Julie D. Saba ◽  
...  
Keyword(s):  
Cord Blood ◽  
Thalassemia Major ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Sibling Donor ◽  
Health History ◽  
Clinical Investigations ◽  
Donor Cells ◽  
Nonmalignant Disease ◽  
Hsc Transplantation

Abstract Banking of cord blood (CB) for unrelated hematopoietic stem cell (HSC) transplantation is well established. However, directed-donor banking of CB for siblings in a current good tissue practices (cGTP) environment has not previously been investigated. Families were eligible for the present study if they were caring for a child with a disorder treatable by HSC transplantation and expecting the birth of a full sibling. We devised standard operating procedures and policies to address eligibility, donor recruitment, donor and recipient evaluation, CB collection, shipping, graft characterization, storage, and release of CB from quarantine. Many of these policies are distinctly different from those established for unrelated-donor CB banks. We enrolled 540 families from 42 states. Collections occurred at several hundred different hospitals. No family was deferred on the basis of health history or infectious disease testing, but departures from standard donor suitability criteria were documented. Disease categories for sibling recipients included malignancy, sickle cell anemia, thalassemia major, nonmalignant hematological conditions, and metabolic errors. Mean CB volume (including anticoagulant) was 103.1 mL; mean nucleated cell count was 8.9 × 108. Cell dose exceeded 1.5 × 107 nucleated cells per kilogram for 90% of banked units. Seventeen units (3.4%) have been transplanted. Sixteen of the 17 CB allograft recipients had stable engraftment of donor cells. Remote-site collection of sibling donor CB can be accomplished with a high success rate and in a cGTP-guided environment. The cellular products have been used successfully for transplantation; their number and characteristics should be adequate to support the first prospective clinical investigations of sibling CB transplantation.

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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