Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor.

Sebrango, Ana; Vicuña, Isabel; Laiglesia, Almudena de; Millán, Isabel; Bautista, Guiomar; Martín-Donaire, Trinidad; Regidor, C; Cabrera, Rafael; Fernández, M.N.

doi:10.1016/j.beha.2010.05.002

Cited by 28 publications

(24 citation statements)

References 44 publications

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“…Several reports have revealed some encouraging results both in myeloablative and non-myeloablative conditioning, which proved the feasibility of this approach. 4,11,20,[24][25][26][27] The Spanish group recently updated the data with a long-term follow-up, which demonstrated outcomes comparable to the outcome achieved with HLA-identical related donors in acute leukemia and myelodysplastic syndromes. 20 The median times to neutrophil and platelet recovery were 11 days and 37 days, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…11,20,25,26 Competition between grafts of various sources is commonly observed after double UCB transplantation, which induces the elimination of one of the grafts. A probable explanation is an immunological graft-versus-graft effect.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15] Although considerable effort has been devoted to address the problem, such as using double units of cord blood, intrabone infusion or co-infusion of expanded cord blood progenitors, [15][16][17][18][19] none has been shown to clearly overcome the obstacles so far. [20][21][22][23] In order to speed up hematopoietic recovery, the team from Universidad Autonoma de Madrid has pioneered a transplantation strategy of myeloablative cord SCT combined with related haploidentical stem cells as a third-party donor support. Several reports have revealed some encouraging results both in myeloablative and non-myeloablative conditioning, which proved the feasibility of this approach.…”

Section: Discussionmentioning

confidence: 99%

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Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Chen

et al. 2013

Bone Marrow Transplant

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We conducted a single-arm prospective study in 50 patients who received the combination of an haploidentical stem cell graft and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. The median time for neutrophil engraftment was 13 days (11-20 days), and for platelets was 15 days (11-180 days). All surviving patients attained complete haploidentical engraftment except three patients who presented a mixed engraftment with increasing cord blood and decreasing haplo mismatch chimerism during the first 4 months after transplantation. The cumulative incidence of grade II-IV acute GVHD was 20% ± 0.327% at day þ 100, and the incidence of chronic GVHD was 19.26% ± 1.0% at 1 year. The 1-year cumulative incidence of relapse was 19.78%±1%, and the TRM was 16.2%±0.54%. At 1 year, overall survival was 78.6%±7.6% and PFS 64.0%±11.0%. The BU/CY-based conditional regimen showed a significant superiority over TBI/CY on PFS (relative risk ¼ 5.012, 95% confidence interval, 1.146-21.927, P ¼ 0.032). In conclusion, the co-infusion of an unrelated cord blood unit may potentially improve the outcome of haploidentical allogeneic hematopoietic SCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Chen

et al. 2013

Bone Marrow Transplant

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“…Their recently updated data demonstrated rapid neutrophil and platelet recovery. 30,31 Initial engraftment by the third-party donor was ultimately superseded by permanent UCB engraftment. Their long-term outcome data were encouraging, but, with a median age of 34 years, their study was restricted to relatively young patients.…”

Section: Discussionmentioning

confidence: 99%

Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions

Liu

Rich

Godley

et al. 2011

Blood

159

129

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We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34 ؉ stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P ‫؍‬ .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800. (Blood. 2011;118(24):6438-6445)

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“…87 The advantage of this approach is the rapid engraftment of the haplo cells to reduce the risk of early infections, followed by sustained hematopoietic engraftment of the UCB. 88 Five-year DFS of 47% has been reported with this strategy.…”

Section: Combination Of Donor Sourcesmentioning

confidence: 99%

Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant

Ballen

Koreth

Chen

et al. 2012

Blood

130

108

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Only 30% of patients who require an allogeneic hematopoietic cell transplant will have an HLA-matched sibling donor. A search for an unrelated donor will be undertaken for patients without a matched family donor. However, many patients, particularly patients of diverse racial and ethnic backgrounds, may not be able to rapidly identify a suitably matched unrelated donor. Three alternative graft sources, umbilical cord blood (UCB), haploidentical (haplo)-related donor, and mismatched unrelated donor (MMUD) are available. UCB is associated with decreased GVHD, but hematologic recovery and immune reconstitution are slow. Haplo-HCT is characterized by donor availability for transplantation and after transplantation adoptive cellular immunotherapy but may be complicated by a high risk of graft failure and relapse. A MMUD transplant may also be an option, but GVHD may be of greater concern. Phase 2 studies have documented advances in HLA typing, GVHD prophylaxis, and infection prevention, which have improved survival. The same patient evaluated in different transplant centers may be offered MMUD, UCB, or haplo-HCT depending on center preference. In this review, we discuss the rationale for donor choice and the need of phase 3 studies to help answer this important question. IntroductionPatient 1 is a 62-year-old woman of Hispanic and Native American descent with a history of breast cancer, treated with surgery and chemotherapy. She is in complete remission; 5 years later, she develops acute myelogenous leukemia (AML) with monosomy 7 karyotype. She attains a complete remission, has an Eastern Cooperative Oncology Group performance status of 1, and reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HCT) is recommended. She has 3 siblings, but none is a HLA full (8/8 HLA-A,-B,-C,-DR) match. One sibling is a haploidentical (haplo) match. Her HLA typing is entered into the National Marrow Donor Program (NMDP), but no fully matched donor is identified. An unrelated donor with a single allele level mismatch at HLA-B is identified. Search of the umbilical cord blood (UCB) registries reveals 2 HLA 4/6 (-A,-B, -DR matches) UCB units with a combined cell dose of 5.3 ϫ 10 7 nucleated cells/kg.Most transplant physicians would agree that the only curative therapy for therapy-related AML is allogeneic HCT, and many would favor an RIC regimen for this patient. However, this patient might be offered a haplo-HCT from her sibling at one transplant center, a double UCB transplant (dUCBT) at a different center, and a mismatched unrelated transplant (MMUD) in another part of the country. All of these options have curative potential but significant mortality and morbidity. How is this patient to decide? What can her hematologists do to assist her?Only 30% of patients will have a matched sibling donor. The NMDP was established in 1986 and now boasts more than 16 million volunteer donors. 1 Today, approximately 60% of white, but only 20% to 45% of black and other minority patients, will be able to find an ...

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Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor.

Cited by 28 publications

References 44 publications

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions

Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant

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