Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts

Avery, Sharon; Shi, Wei; Lubin, Marissa; Gonzales, Anne Marie; Heller, Glenn; Castro‐Malaspina, Hugo; Giralt, Sergio; Kernan, Nancy A.; Scaradavou, Andromachi; Barker, Juliet N.

doi:10.1182/blood-2010-08-300491

Cited by 120 publications

(143 citation statements)

References 35 publications

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“…Although a relatively small number of patients was included in this trial, the use of CD34-selected cells from a haploidentical related-donor is associated with similar rates of primary engraftment (90%) to than seen following double UCB transplants (86-93%). 24,25 Furthermore, neutrophil recovery appeared faster with haploidentical HCT (median ¼ 13 days, range: 9-15 days) when compared with double UCB transplants (median ¼ 23-25 days). 24,25 Platelet engraftment was also rapid following haploidentical HCT (median ¼ 16 days, range: 12-19 days).…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Furthermore, neutrophil recovery appeared faster with haploidentical HCT (median ¼ 13 days, range: 9-15 days) when compared with double UCB transplants (median ¼ 23-25 days). 24,25 Platelet engraftment was also rapid following haploidentical HCT (median ¼ 16 days, range: 12-19 days). Although haploidentical HCT has been associated with slow immune recovery, in our study the median time to recovery of CD4 cells to 40.2 Â 10 9 /L was 5.2 months, and a median normal (450% control) PHA response was seen at 7.9 months.…”

Section: Discussionmentioning

confidence: 99%

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Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Dvorak

Horn

et al. 2012

Bone Marrow Transplant

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We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34 þ -cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34 þ cells (median: 22 Â 10 6 /kg) with a fixed dose of 3 Â 10 4 /kg CD3 þ cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15-54%) of evaluable patients, there was no grade III-IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17-59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48-83%) with a median survivor follow-up of 49 months (range: 18-119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56-100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22-89%). Megadose CD34 þ cells with a fixed CD3 þ cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Dvorak

Horn

et al. 2012

Bone Marrow Transplant

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“…29 In the double CB transplantation setting using reduced intensity conditioning regimen, the number of infused T cells seems to be also associated with enhanced engraftment and unit dominance. 30 Moreover, early T cells chimerism predicts the long-term engrafting unit in the double CB setting. 24 Similarly, our findings show that a high early posttransplantation CB T cells chimerism, and more importantly, an increasing T cells chimerism dynamics between days þ 14 and þ 21, correlates with long-term CB engraftment.…”

Section: Discussionmentioning

confidence: 99%

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

Kwon

Martínez-Laperche

Balsalobre

et al. 2013

Bone Marrow Transplant

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Single-unit umbilical cord blood (CB) SCT is limited by low total nucleated cell (TNC) dose. Co-infusion of CD34 þ cells from a third party HLA-mismatched donor, known as dual or haplo-cord transplant, reduces the period of post-transplant neutropenia and related complications. The aim of this study was to analyze the value of early post-transplant peripheral blood (PB) and T cell chimerism after 28 dual transplants regarding CB engraftment. Cumulative incidence of myeloid engraftment at 30 days was 93% with a median time to engraftment of 14 days (10-29). Patients who developed CB graft failure (n ¼ 5) showed very low percentages of CB cells on days þ 14, þ 21 and þ 28 with decreasing dynamics. On the other hand, percentages of CB cells in patients who achieved CB engraftment increased over time. Interestingly, such patients showed two distinct chimerism dynamics in PB, but all of them showed a predominance of CB T cells early after SCT with increasing dynamics over time. Early post-transplant chimerism dynamics in PB and T cells predicts CB graft failure enabling rapid therapeutic measures to be applied. On the other hand, early increasing percentages of CB T cells correlates with ultimate CB engraftment.Bone Marrow Transplantation (2014) 49, 212-218; doi:10.1038/bmt.2013.177; published online 11 November 2013Keywords: cord blood transplantation; haploidentical donor; chimerism; graft failure INTRODUCTION Unrelated umbilical cord blood (CB) has been increasingly used as an alternative stem cell source for adult patients eligible for allogeneic SCT, but lacking HLA-matched adult donors. [1][2][3] However, one of the main limitations of CB transplantation is the late engraftment related to low total nucleated cell (TNC) dose, with the subsequent increased risk of serious early neutropenia-related infections and high non-relapse mortality. 2,4 Single CB transplantation supported by mobilized and selected CD34 þ cells from a HLA-mismatched third party donor (TPD), known as dual or haplo-cord SCT, has shown to reduce the period of post-transplant neutropenia and related early morbidity and mortality associated with single CB transplantation. [5][6][7][8] This strategy offers a rapid neutrophil recovery at the expense firstly of TPD cells with subsequent replacement and long-term engraftment of CB cells.Graft failure and graft rejection are major complications after allogeneic SCT, with a frequency as high as 23% using CB transplants. 9-11 Outcome of patients who develop graft failure without a second transplantation is dismal with survival rates lower than 10%; 12 however, survival rates improve significantly to 30-60% after salvage transplantation using reduced intensity conditioning regimens. [13][14][15] From the extensive experience with CB transplantation, various risk factors have been associated with CB graft failure. [16][17][18] Once transplantation has been performed, early detection of graft failure is important to start rapid therapeutic measures such as immunomodulation and to launch a second transplan...

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“…As stated in previous sections, based on the importance of HLA match demonstrated in large analyses of single-unit CBT, 17 and a recent MSKCC analysis of 84 double-unit CBT recipients, 28 our institutional policy is to give a strong priority to HLA match above a TNC threshold of ϳ 2.0 ϫ 10 7 /kg for each unit of a double-unit graft. Further, the Avery analysis demonstrated no relationship between unit-unit HLA match and the likelihood of sustained donor engraftment.…”

Section: Hla Match and Double-unit Graft Selectionmentioning

confidence: 99%

“…84 double-unit CBT recipients at MSKCC, 28 we give a strong priority to HLA match above a precryopreservation TNC threshold of ϳ 2.0 ϫ 10 7 /kg for each unit of a double-unit graft. This approach gives strong priority to HLA match but augments the chance of engraftment by infusing 2 units with an at least adequate dose in each unit.…”

Section: Tnc/kg and Selection Of Double-unit Graftsmentioning

confidence: 99%

How I treat: the selection and acquisition of unrelated cord blood grafts

Barker

Byam

Scaradavou

2011

Blood

Self Cite

144

112

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Use of unrelated donor cord blood (CB) as an alternative stem cell source is increasing, and yet there is little information to guide transplant centers in the unique aspects of the search and selection of CB grafts. There is no mechanism to easily access the global inventory of CB units, nor is the product information provided by all banks standardized. To address these challenges, this manuscript reviews the logistics of the search, selection process, and acquisition of CB grafts as practiced by our center. Topics include who should be considered for a CB search, how to access the global CB inventory, and how to balance total nucleated cell dose and human leukocyte antigen match in unit selection. We discuss aspects of unit quality and other graft characteristics (processing methods, unit age, availability of attached segments, infectious disease, and hemoglobinopathy screening) to be considered. We incorporate these considerations into a unit selection algorithm, including how to select double-unit grafts. We also describe how we plan for unit shipment and the role of backup grafts. This review aims to provide a framework for CB unit selection and help transplantation centers perform efficient CB searches. (Blood. 2011;117(8):2332-2339) IntroductionUnrelated donor cord blood transplantation (CBT) has become a widely accepted treatment for lethal hematologic diseases. Both the number of CB transplantations 1 and the global inventory of CB units (estimated at 400 000) 2 are growing rapidly. Therefore, it is critically important that transplantation centers (TCs) have a thorough understanding of how to perform a CB search as well as the challenges encountered in the selection and acquisition of CB grafts. This article is a practical guide for the TCs, especially those new to the field of CBT, and is based on our daily experience of searching the global CB inventory, our knowledge of CB banking and CB testing standards, and evaluation of recently published data. Thus, we outline our search practices at Memorial SloanKettering Cancer Center (MSKCC). Who should get a formal CB search with confirmatory HLA typing of CB unitsThere is a progressive decrease in post-transplantation survival with each human leukocyte antigen (HLA) or allele mismatch at HLA-A, -B, -C, -DRB1 loci of adult unrelated donor (URD) grafts, with donor-recipient HLA-DQ disparity being detrimental when present with other mismatches. 3 Therefore, TCs must decide what level of HLA disparity will be tolerated with a URD before alternative hematopoietic stem cell sources such as CB are sought. In addition, as CB grafts are available faster than URD, 4 transplantation urgency may be an additional reason to use CB. Prolonged URD searches are unlikely to result in acquisition of a suitably matched URD if one is not identified early in the search. 5,6 Knowledge of the patient's ancestry is critical given that patients from racial and ethnic minorities (including all those with nonEuropean ancestry) frequently do not have suitably matched URDs, 7 a result...

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Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts

Cited by 120 publications

References 35 publications

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34+ cells and a fixed CD3+ dose

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

How I treat: the selection and acquisition of unrelated cord blood grafts

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