Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols

Hough, Rachael; Danby, Robert; Russell, Nigel H.; Marks, David I.; Veys, Paul; Shaw, Bronwen E.; Wynn, Rob; Vora, Ajay; Mackinnon, Stephen; Peggs, Karl S.; Crawley, Charles; Craddock, Charles; Pagliuca, Antonio; Cook, Gordon; Snowden, John A.; Clark, Andrew; Marsh, Judith; Querol, Sergio; Parkes, Guy; Braund, Henny; Rocha, Vanderson

doi:10.1111/bjh.13802

Cited by 74 publications

(69 citation statements)

References 42 publications

(27 reference statements)

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“…CMV status) donors is available, nonpermissive mismatches should be minimized (Grade 2C) For mismatched related and unrelated donor selection, HVG mismatches are favoured over bidirectional and GVH mismatches (Grade 2C) UCB units should be HLA typed to high‐resolution HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 (Grade 1B) Selection of UCB units should follow national consensus guidelines published by Hough et al . () (Grade 1A) HLA alloantibody testing of the recipient should be performed at the time of donor search and should be repeated at the time of donor work‐up request if an HLA‐mismatched donor is selected (Grade 1A) The clinical team must be made aware of any HLA alloantibody incompatibility for a selected donor (Grade 1A) When a choice of equally well‐matched donors is available, avoid selection of donors against which the patient has HLA alloantibodies (Grade 1A) HLA alloantibody testing should be performed in cases of failed engraftment if the donor is HLA mismatched (Grade 1B) The guideline published by Emery et al . () recommending CMV matching between patient and donor should be followed (Grade 1A) Major ABO incompatibilities should be avoided when there is a choice of HLA‐ and CMV‐matched donors (Grade 1A) Male donors should be preferentially chosen where the patient has multiple HLA‐, CMV‐ and ABO‐matched donors (Grade 1C) Younger donors should be preferentially selected (Grade 1B) Homozygosity and novel HLA alleles identified within DNA extracted from patients with a high frequency of circulating tumour cells should be confirmed by family studies or using DNA extracted from nondiseased cells (Grade 2A) Individuals actively involved in the provision of a donor selection service should undertake CPD, and the service should be directed by a RCPath Fellow and Consultant in H&I (Grade 1A)…”

Section: List Of Recommendationsmentioning

confidence: 99%

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BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

Little

Green

Harvey

et al. 2016

Int J Immunogenetics

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List of recommendations• All laboratories performing H&I testing for allogeneic HPC transplantation should follow EFI standards and be accreditated by EFI and UKAS/CPA. (Grade 1A)• HLA typing definitions as described by Nunes et al. 2011 and here should be used (Grade 1A)• HLA typing results should use official WHO HLA Nomenclature (Grade 1A)• The clinical urgency should be made available to the individual performing the related and unrelated donor search (Grade 1B)• HLA high resolution typing should be performed on potential matching; mismatching and haploidentical related donors when familial haplotypes cannot be fully assigned (Grade 1A)• Patients and selected related donors should be typed for HLA-A, -B, -C, -DRB1 and -DQB1 (+/-DPB1) (Grade 1A).• All patients and donors must have their HLA type confirmed on a second sample pre-transplant (Grade 1A).• The patient should be high resolution typed prior to submitting the HLA type for an unrelated donor search (Grade 1A)• A 10/10 high resolution HLA-A, -B, -C, -DRB1 and -DQB1 matched unrelated PBSC or bone marrow donor should be used where possible (Grade 1A).• Where a 10/10 matched PBSC or bone marrow donor is not available a single mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 is acceptable (Grade 1A).• Alternative progenitor cell donors (cord blood or haplo-identical) should be considered early in the donor search when a patient is unlikely to have an HLA matched unrelated donor (Grade 1A).• HLA-DRB3, -DRB4, -DRB5 typing should be performed and, when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, mismatches for these should be minimized (Grade 2A). • For unrelated donor selection, HLA-DPB1 typing should be performed and when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, non-permissive mismatches should be minimised (Grade 2C).• For mismatched related and unrelated donor selection, HVG mismatches are favoured over bi-directional and GVH mismatches (Grade 2C).• UCB units should be HLA typed to high resolution HLA-A, -B, -C, -DRB1, -DQB1 (Grade 1B ).• Selection of UCB units should follow national consensus guidelines published by Hough et al. (Grade 1A).• HLA alloantibody testing of the recipient should be performed at the time of donor search and should be repeated at the time of donor work-up request if an HLA mismatched donor is selected (Grade 1A).• The clinical team must be made aware of any HLA alloantibody incompatibility for a selected donor (Grade 1A).• When a choice of equally well matched donors is available, avoid selection of donors against which the patient has HLA alloantibodies (Grade 1A).• HLA alloantibody testing should be performed in cases of failed engraftment if the donor is HLA mismatched (Grade 1B).• The guideline published by Emery et al., 2013 recommending CMV matching between patient and donor should be followed (Grade 1A).• Major ABO incompatibilities should be avoided when there is a choice of HLA and CMV matched donors (Grade 1A)• Male donors ...

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Section: List Of Recommendationsmentioning

confidence: 99%

“… UCB units should be HLA typed to high‐resolution HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 (Grade 1B). Selection of UCB units should follow national consensus guidelines published by Hough et al . () (Grade 1A). …”

Section: Selection Of Unrelated Umbilical Cord Blood Unitsmentioning

confidence: 99%

BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

Little

Green

Harvey

et al. 2016

Int J Immunogenetics

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“…Mounting experience with unrelated UCB transplantation (UCBT), modifications of conditioning regimens, and better choice of the UCB unit according to cell dose and HLA typing have led to improved outcomes (2). Various studies have linked individual parameters such as recipient's disease status, cell dose, degree of HLA match, graft type (single vs. double), and anti-thymocyte globulin (ATG) administration with mortality following UCBT (3)(4)(5)(6)(7)(8)(9)(10)(11). However, it remains unclear how these parameters should be best combined to optimize transplantation outcomes and obtain prognostic information.…”

Section: Introductionmentioning

confidence: 99%

An Integrative Scoring System for Survival Prediction Following Umbilical Cord Blood Transplantation in Acute Leukemia

Shouval

Ruggeri

Labopin

et al. 2017

Clinical Cancer Research

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Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free survival (LFS) at 2 years following UCBT in AL patients.Experimental Design: The study cohort included 3,140 pediatric and adult AL UCBT patients from the European Society of Blood and Marrow Transplantation and Eurocord registries. Patients received single or double cord blood units. The dataset was geographically split into a derivation (n ¼ 2,362, 65%) and validation set (n ¼ 778, 35%). Top predictors of OS were identified using the Random Survival Forest algorithm and introduced into a Cox regression model, which served for the construction of the UCBT risk score. Results:The score includes nine variables: disease status, diagnosis, cell dose, age, center experience, cytomegalovirus serostatus, degree of HLA mismatch, previous autograft, and antithymocyte globulin administration. Over the validation set an increasing score was associated with decreasing probabilities for 2 years OS and LFS, ranging from 70.21% [68.89-70.71 Conclusions: The UCBT score is a simple tool for risk stratification of AL patients undergoing UCBT. Widespread application of the score will require further independent validation. Clin Cancer Res; 23(21); 6478-86. Ó2017 AACR.

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“…The double UCB transplantation platform has helped overcome the barrier of low cell dose in adult patients who do not have an adequately sized single unit and resulted in improved engraftment rates 4 . However, treatment related mortality (TRM) remains elevated using this platform including a rapid early rise in TRM to over 30% at 6 months, suggestive of excessive toxicity associated with the standard myeloablative total body irradiation (TBI), fludarabine, and cyclophosphamide regimen 5, 6 . For patients with high risk hematologic malignancies undergoing UCB transplantation, a myeloablative regimen is needed that exerts potent anti-tumor activity and facilitates reliable engraftment while still minimizing toxicity.…”

Section: Introductionmentioning

confidence: 99%

Adult Umbilical Cord Blood Transplantation Using Myeloablative Thiotepa, Total Body Irradiation, and Fludarabine Conditioning

Anand

Thomas

Corbet

et al. 2017

Biology of Blood and Marrow Transplantation

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Treatment related mortality (TRM) remains elevated in adult patients undergoing umbilical cord blood (UCB) transplantation, including an early rise in TRM suggestive of excessive toxicity associated with the standard myeloablative total body irradiation (TBI), fludarabine, and cyclophosphamide regimen. In an attempt to reduce regimen-related toxicity, we previously studied a modified myeloablative regimen with total body irradiation (1350 cGy) and fludarabine (160 mg/m2); TRM was decreased but neutrophil engraftment was suboptimal. Therefore, in order to improve engraftment while still minimizing regimen-related toxicity, we piloted a myeloablative regimen with the addition of thiotepa (10 mg/kg) to TBI and fludarabine conditioning. Thirty-one adult patients (median age 46 years; range, 19–65) with hematologic malignancies (acute leukemia/MDS 77%, lymphoid malignancy 23%) underwent single (n=1) or double (n=30) UCB transplantation from 2010 to 2015 at our institution. The cumulative incidence (CI) of neutrophil engraftment was 90% (95% CI, 70–97%) by 60 days, with a median time to engraftment of 21 days (95% CI, 19–26 days). The CI of platelet engraftment was 77% (95% CI, 57–89%) by 100 days, with a median time to engraftment of 47 days (95% CI, 37–73 days). Cumulative incidences of grades II–IV and grades III–IV acute GVHD at day 100 were 45% (95% CI, 27–62%) and 10% (95% CI, 2–23%), respectively. The overall incidence of chronic GVHD at 2 years was 40% (95% CI, 22–57%), with 17% (95% CI, 6–33%) of patients experiencing moderate to severe chronic GVHD by 2 years. Treatment-related mortality at 180 days was 13% (95% CI, 4–27%), while at 1 year was 24% (95% CI, 10–41%) and at 3 years was 30% (95% CI, 13–49%). Relapse at 1 year was 13% (95% CI, 4–27%) and at 3 years was 19% (95% CI, 6–38%). With a median follow-up of 35.5 months (95% CI, 12.7–52.2 months), disease-free and overall survival at 3 years was 51% (95% CI, 29–69%) and 57% (95% CI, 36–73%), respectively. This regimen represents a reasonable alternative to myeloablative conditioning with TBI, fludarabine, and cyclophosphamide and warrants further study.

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Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols

Cited by 74 publications

References 42 publications

BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

An Integrative Scoring System for Survival Prediction Following Umbilical Cord Blood Transplantation in Acute Leukemia

Adult Umbilical Cord Blood Transplantation Using Myeloablative Thiotepa, Total Body Irradiation, and Fludarabine Conditioning

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